科学网—标签 - 艾滋病病毒

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crossludo 2012-7-16 17:43

中国研发艾滋病毒疫苗新制法在果蝇上试验成功核心提示：艾滋病治疗是世界难题，能否通过疫苗来控制ＨＩＶ的传播？上海科研人员近日在艾滋病病毒Ｉ型疫苗的研发上取得突破性成果，探索出新的疫苗制备方法，并首次在果蝇细胞上试验成功。艾滋病治疗是世界难题，能否通过疫苗来控制ＨＩＶ的传播？上海科研人员近日在艾滋病病毒Ｉ型疫苗的研发上取得突破性成果，探索出新的疫苗制备方法，并首次在果蝇细胞上试验成功。该研究成果在国际知名杂志《病毒学杂志》在线发表。中科院上海巴斯德研究所研究员周保罗带领的研究组找到了疫苗制备方法的突破口——被称为 “空心杀手” 的“病毒样颗粒”。该颗粒没有艾滋病病毒核酸，不能自主复制，但在形态上却与真正的艾滋病病毒粒子相同，如果能在进人体后让人产生相应抗体，进而使人体能对艾滋病毒免疫，那就意味着艾滋病病毒疫苗的研发取得了成功。在哪个对象上进行试验又是一道难题。周保罗选择的是果蝇，相比鼠、猴，又是一次创新。经过多年研究，终于取得良好效果。周保罗介绍说，用传统疫苗制备方法试验存在病毒污染、各批次不稳定、蛋白剪切难度等问题，新方法已将它们逐一克服。在果蝇试验后，周保罗再以鼠、猴为对象进行验证。目前小鼠体内已产生抗体反应，下一步将在猴子身上进行“攻毒”试验。如果猴子能够产生对艾滋病毒免疫抗体，就可以为最终的人体试验的成功铺平道路。 “如果猴子试验能达到预期效果的话，接下来就做人临床试验，分一二三期，一般至少五年到十年。”周保罗说。这也就意味着，如果一切顺利的话，届时，艾滋病毒疫苗的最终问世便有了坚实的基础。

个人分类: 医学前沿|1169 次阅读|0 个评论

[转载]中国科研人员研发艾滋病病毒疫苗取得重要成果

xuxiaxx 2012-7-16 15:16

艾滋病治疗是世界难题，能否通过疫苗来控制ＨＩＶ的传播？上海科研人员近日在艾滋病病毒Ｉ型疫苗的研发上取得突破性成果，探索出新的疫苗制备方法，并首次在果蝇细胞上试验成功。　　该研究成果在国际知名杂志《病毒学杂志》在线发表。　　中科院上海巴斯德研究所研究员周保罗带领的研究组找到了疫苗制备方法的突破口——被称为“空心杀手”的“病毒样颗粒”。该颗粒没有艾滋病病毒核酸，不能自主复制，但在形态上却与真正的艾滋病病毒粒子相同，如果能在进人体后让人产生相应抗体，进而使人体能对艾滋病毒免疫，那就意味着艾滋病病毒疫苗的研发取得了成功。　　在哪个对象上进行试验又是一道难题。周保罗选择的是果蝇，相比鼠、猴，又是一次创新。经过多年研究，终于取得良好效果。　　周保罗介绍说，用传统疫苗制备方法试验存在病毒污染、各批次不稳定、蛋白剪切难度等问题，新方法已将它们逐一克服。　　在果蝇试验后，周保罗再以鼠、猴为对象进行验证。目前小鼠体内已产生抗体反应，下一步将在猴子身上进行“攻毒”试验。如果猴子能够产生对艾滋病毒免疫抗体，就可以为最终的人体试验的成功铺平道路。　　“如果猴子试验能达到预期效果的话，接下来就做人临床试验，分一二三期，一般至少五年到十年。”周保罗说。这也就意味着，如果一切顺利的话，届时，艾滋病毒疫苗的最终问世便有了坚实的基础。来源：中国科技网

1301 次阅读|0 个评论

乌鲁木齐艾滋病病毒感染人数全疆居第二

热度 2 gaojiange 2012-5-15 21:01

乌鲁木齐市去年新增报告艾滋病病毒感染者和艾滋病病人1312例，死亡136例。其中，性接触传播艾滋病的比例明显上升，感染者配偶、男男性行为人群感染率上升较快。　截至去年12月31日，乌鲁木齐市累计报告艾滋病病毒感染者和艾滋病病人共10536例，累计死亡997例。累计报告感染人数位居全疆第二位。吸毒和性传播并存成为主要传播途径，吸毒人群、男男性接触者等高危人群综合干预覆盖面不足，共用针具吸毒比例仍较高。艾滋病疫情已开始从高危人群向一般人群扩散。

个人分类: 天山南北【幽幽西部】|2671 次阅读|3 个评论

[转载]世卫组织强调结核病与艾滋病治疗相结合的重要性

xuxiaxx 2012-3-7 16:53

世界卫生组织２日在日内瓦表示，２００６年至２０１１年间，各国医疗部门将结核病防治与艾滋病治疗相结合，挽救了９１万名同时感染艾滋病病毒的结核病患者的生命。　　世卫组织当天在日内瓦发布了新的全球结核病与艾滋病联合预防、诊断和治疗政策，这份文件建议各国对结核病患者、结核病疑似患者及其密切接触人群进行例行的艾滋病病毒检测；为同时感染艾滋病病毒的结核病患者提供廉价、有效的药物复方新诺明，防止出现肺部感染症状；对感染艾滋病病毒的结核病患者应在开始治疗结核病的头两周提供抗逆转录病毒治疗药物。　　当天在日内瓦举行的记者会上，世卫组织艾滋病防治司司长戈特弗里德呼吁各国将结核病防治工作与艾滋病治疗工作相结合。他强调，各国在过去几年的实践表明，这一做法行之有效，确实可以挽救生命。　　据世卫组织介绍，艾滋病和结核病是相互促进病变进展、迅速导致病人死亡的伴发病。艾滋病病毒携带者若同时感染结核病的细菌后，患结核病的可能性是正常人的３４倍。２０１０年，全球有１１０万艾滋病病毒携带者患有结核病，其中八成在非洲。从全球情况看，１２％的结核病人患有艾滋病病毒合并感染。来源：新华网

1638 次阅读|0 个评论

[转载]艾滋病防治新型阴道凝胶临床实验被叫停

xuxiaxx 2011-11-29 09:31

艾滋病防治研究遭遇重大挫折，针对一种被认为能够降低艾滋病病毒(HIV)感染风险的新型阴道凝胶的临床实验已经被叫停，因为此前的研究表明这种凝胶是无效的。　　来自由美国国立卫生研究院创立的杀菌剂实验网络的研究人员对这一结果表示惊讶，因为此前针对含有药物替诺福韦凝胶的一项研究得出了振奋人心的结果。　　南非艾滋病规划研究中心进行的首次实验表明，在使用了替诺福韦凝胶的女性中，艾滋病感染率降低了3g%，在定期使用这种凝胶的女性中，感染率降低了54%。　　在2010年公布的上述结果令人们看到了希望：一种新型凝胶可以减缓艾滋病的传播，最终为女性提供一种自我保护的突破性方法。　　观察人士曾经希望，一项缩写为VOICE(控制艾滋病的阴道和口腔干预)的研究将印证上述发现。这一研究始于2009年9月，研究的进行得到了南非、乌干达和津巴布韦三国的5000名女性的帮助。　　然而，一个独立的数据和安全监督委员会对VOICE项目所进行的临时评估确定，替诺福韦凝胶的疗效甚至不如安慰剂。这项研究的部分内容目前已经被取消。　　研究人员沙伦·希利尔和伊恩·麦高恩写道：“就目前而言，这项研究将继续进行，我们将完成对继续参与研究的妇女的疗效间访工作。我们都急切地想要弄清楚，坚持用药、我们的日常剂量安排、炎症或其他因素是否能够解释，在VOICE项目中，替诺福韦在口腔和阴道中的应用为何缺乏疗效。我们不大可能在明年晚些时候之前完成所有化验分析。’ 　　希利尔说，她对研究结果感到“意外和失望”。这些研究人员说，他们必须要等到剩下的实验结束才能进行更加全面的分析。　　南非艾滋病规划研究中心主任、VOICE实验的区域负责人萨利姆·阿卜杜勒·卡里姆坦承对这样的结果感到非常失望。他说：“这些结果完全出人意料，因为来自实验室研究、动物实验和临床实验的诸多证据表明，替诺福韦凝胶能够预防HIV感染。然而，科学并不总是能够得出我们希望的结果。” 来源：新华网

1079 次阅读|0 个评论

[转载]报告称全球艾滋病病毒携带者达3400万创下新高

xuxiaxx 2011-11-23 15:35

据新华社电联合国艾滋病规划署执行主任米歇尔·西迪贝在位于瑞士城市日内瓦的总部发布年报，全球 2010 年艾滋病病毒携带者总数大约 3400 万人，比 2009 年增加 70 万。　　西迪贝说，感染者总数上升是因为去年全球就医人数增加，特别是中低收入国家因艾滋病病毒死亡的人数减少。　　艾滋病规划署报告显示，中低收入国家去年 1420 万就医者中，大约 660 万人正接受治疗，占总数 47% ，比 2009 年高 11 个百分点。　　一家国际扶贫组织的工作人员阿德里安·洛维特说，全球艾滋病病毒携带者就医人数去年增加大约 140 万。他说，这显示“巨大进步”，同时需进一步努力以“扭转局势”。　　艾滋病规划署统计，全球去年大约 180 万人死于艾滋病相关原因，比 2006 年高峰值减少 40 万，大约 70 万人因接受治疗得以幸存。自 1995 年以来，中低收入国家大约 250 万艾滋病病毒携带者因就医免于死亡。除艾滋病病毒携带者就医人数增加、死亡人数减少外，全球 2010 年新感染艾滋病病毒人数同样下降。报告显示，全球去年艾滋病病毒携带者新增大约 270 万，比 2001 年减少 15% ，比 1997 年高峰值减少 21% 。 “转折年” 西迪贝以“转折年”描述艾滋病规划署 2010 年成果。他说，“尽管（欧洲一些国家遭遇）公共财政危机，（艾滋病规划署）资金来源面临不确定性，我们看到了结果，看到更多国家有效降低新增感染人数”，遏制病毒传播势头。报告说，艾滋病防治地区差异依然明显，非洲和亚洲部分地区仍是“重灾区”。以撒哈拉以南非洲为例，全球大约 70% 新增感染者来自这一地区，艾滋病病毒相关病因死亡人数接近全球总数一半。国际医疗人道援助组织“无国界医生”执行主管提多·冯·舍恩—安格尔说：“一些 " 重灾区 " 国家的政府希望依科学行事，抓住时机，扭转艾滋病传播趋势。不过，如果资金不到位，一切都是空谈。” 来源：新华网

1791 次阅读|0 个评论

[转载]养生新知：研究称艾滋病患者寿命有望延长15年

xuxiaxx 2011-10-18 08:36

艾滋病是一种病死率极高的传染病。感染了艾滋病病毒的人，按照医学界20世纪90年代的估计，一般只能再存活7~10年的时间，但近年情况已发生改变，艾滋病患者的平均寿命已大大延长。英国独立报日前报道：“在英国通过一项新的研究统计表明，艾滋病感染者的预期寿命比以往任何时候都高”。据该报道称，新的研究表明，在过去十年中，英国艾滋病患者的寿命有望延长15年。这项研究是由来自英国各医疗机构和学术机构，包括大学、艾滋病服务部门、医院和NH信托的研究人员共同研究出来的。由英国医学研究理事会发起的研究，并在同行评审的英国医学杂志发表。此研究成果，是基于对超过17000名成年艾滋病感染者进行的数据统计而得出的。这些人，进行了艾滋病毒抗逆转录病毒药物治疗（这项治疗现在已成为减缓病毒进展的治疗标准），通过分析这些人的死亡的数据，研究人员估计，在1996年20岁的艾滋病感染者，将有望活到平均年龄50岁，但到2008年，本组平均年龄近66岁的预期寿命。研究人员还发现，如果感染者尽早进行抗逆转录病毒治疗，相比病情恶化后才治疗，可以获得的预期寿命会长很多。这项研究称，这十年来，英国艾滋病患者的预期寿命平均增长了至少15年，主要得益于医药技术和医疗综合治疗条件的提高，艾滋病感染者的预期寿命才得以明显增长。研究还发现，女性艾滋病患者的平均寿命比男性要长10年以上，专家把其原因归结于，女性在怀孕时的验血检查，有助于艾滋病病毒的早期发现，而早发现，早治疗，对延长艾滋病感染者的生命至关重要。英国有将近4万名艾滋病感染者，其中1/4的人对自己的病情一无所知。来源： http://www.qqyy.com/jibing/pfxb/111017/3fb6d.html

1720 次阅读|0 个评论

眼泪是艾滋病病毒新“据点”

热度 2 wdh022 2011-9-12 23:59

北京协和医院感染内科李太生教授等经过长达6年研究，在国际上率先报道称，长期接受鸡尾酒治疗后血液中艾滋病病毒（HIV）已呈阴性的艾滋病患者，其泪液中仍有较高的HIV病毒载量。研究结果提示，泪腺、泪液及相关的组织、器官很可能是HIV病毒的新“据点”。该研究相关论文近日发表在国际著名的《艾滋病》杂志上，引起国际上广泛关注。据介绍，2005年，北京协和医院感染内科、眼科专家首先发现在艾滋病患者的眼部前房水中存有HIV病毒载量。因不清楚房水和泪液的区别，部分媒体在当年报道中曾出现“泪液中发现艾滋病病毒”的提法。但这一误报却引发艾滋病专家新的思考：经成功的鸡尾酒治疗后，艾滋病患者在血液HIV呈阴性的情况下，泪液中究竟有没有HIV病毒载量？沿着这一思路，李太生等进行了国际上首个针对艾滋病患者泪液中HIV病毒载量的定量分析。李太生等以16名长期接受鸡尾酒治疗、外周血HIV病毒呈阴性的艾滋病患者为研究组，2名新诊断但未经治疗、3名治疗后产生耐药的患者为对照组展开研究。在艾滋病专科护士的协助及21位患者知情同意和配合下，研究人员非常艰难地取到了每位患者1毫升以上的泪液，用国际上通用的病毒载量检测、聚合酶链式反应（PCR）等多种方法，选取4个不同的基因点位同时开展检测，结果发现，研究组和对照组泪液中的HIV病毒载量无差异，为200拷贝/毫升~20000拷贝/毫升，远高于正常值（50拷贝/毫升以下）。这一发现提示，除了CD4阳性的T淋巴细胞、巨噬细胞等已发现的艾滋病病毒“储藏库”，泪腺、泪液及相关的组织、器官很可能是HIV病毒的新“据点”，HIV极可能通过泪液发生传染。李太生提醒医护人员，在对HIV阳性患者进行眼部检查或手术时要加强防护、谨慎处理。（来源：健康报段文利）点评：有评论称为什么不认为是眼泪在排毒呢？非常好的思路，是否可以考虑，如果以上结论成立的话，可以考虑采用眼泪疗法，即让患者每天流足够多的眼泪以减少病毒量。有条件的研究者可以考虑实验，同理，可以运用于尿液或者汗液或者其他的一些疾病的排毒中。类似于萃取效应。由此而引申，是否可以采用萃取疗法，目前类似的疗法有刮痧、拔罐、发烧了喝水、排毒养颜等，但是科学而系统的研究似乎不多。此外，是否可以考虑眼部用药，这样更有针对性。

3160 次阅读|3 个评论

茶道养生何须魏帝一丸药，且尽卢仝七碗茶。

xupeiyang 2011-9-1 08:33

中国几千年的中医文化源远流长，“茶道养生”成为中国人追求健康的思维概念。中华食谱各自独特的养生元素，家喻户晓的茶文化，茶叶含有大量的有益成份，茶多酚能抑制癌细胞、抗菌杀菌和抑制病毒等。正如宋代诗人苏轼所言：“何须魏帝一丸药，且尽卢仝七碗茶。”也就是说经常饮茶胜过服药。

个人分类: 长寿秘诀|5254 次阅读|0 个评论

[转载]科学网：研究解开艾滋病病毒无法根除之谜

fqng1008 2011-8-24 09:00

图为一个已被艾滋病病毒感染的供体细胞（绿色），正在感染正常细胞（红色）。（图片提供：Benjamin K. Chen，Mount Sinai School of Medicine）由加州理工学院生物学教授、诺奖获得者大卫·巴尔的摩（David Baltimore）领导的一个研究团队近日发现，艾滋病病毒会利用已感染细胞来接近健康细胞，从而实现病毒大批量传播，这可能是艾滋病病毒在经过抗逆转录病毒药物成功治疗后，仍能在少数受感染细胞中存活的原因。相关研究论文已发表在8月17日的《自然》杂志上。目前，艾滋病病毒感染细胞有两种方式：一是无细胞传播，即病毒在血浆中移动，遭遇免疫系统细胞（T细胞）时，对其传染；二是细胞间传播，病毒以被感染的供体细胞作为媒介在细胞间传播。一旦发现未受感染的靶细胞，供体细胞便将病毒传染给该细胞。研究小组分别使用细胞外艾滋病病毒和供体细胞来感染靶细胞。使用的供体细胞缺少一种天然标记HLA-A2，而靶细胞则有这种标记，这将有助科学家分清两种细胞。结果显示，无论是否有抗病毒药物作用，靶细胞都会被感染。研究人员发现，通过无细胞传播方式感染的细胞在抗病毒药物作用下，数目急剧下降，而即使在大剂量药物的作用下，通过细胞间传播感染的细胞依然是缓慢减少。“我们发现，细胞间传播使更多病毒作用于一个细胞，”该小组成员Alex Sigal说，“这使得病毒存活的几率大大增加。”这或许能解释，为什么抗病毒药物无法根除艾滋病病毒感染。药物治疗本质上说是一种概率性杀毒，即它们不能100%地杀死病毒。所以，当病毒数量变多时，其存活并感染下一个细胞的几率变大。另一个可能是艾滋病病毒进入潜伏期，病毒潜伏在细胞的DNA中，聚集成一个病毒库，不发生复制作用，因而药物对其无效。Sigal表示，这两种方式可能存在相互影响。 “确定病毒的细胞间复制是否导致艾滋病病毒库的产生，对研究治疗方案尤为重要”，他说，“我们不能用对付病毒库的方式来对付（细胞间复制）。”理论上来说，通过激活潜伏病毒库中的病毒，有助实现病毒的根除，但如果病毒进入新细胞内，它们将变得难以对付。 “我们下一步要做的是，从生理学水平上了解艾滋病病毒是怎样通过细胞间传播来感染像淋巴结这样的器官，”Sigal说。（科学网徐文杰/编译）

个人分类: 比较医学|1716 次阅读|0 个评论

国际科研动态与进展 8月22日

xupeiyang 2011-8-22 13:09

近日，在基因组、艾滋病、认知、芯片、等方面取得研究成果。 ----许博主中国著名留美女教授最新Cell文章 (8-22) · F1000：最值得关注的基因组研究 (8-22) · Nature：研究解开艾滋病病毒无法根除之谜 (8-22) · 日本研制出可散发鼠类天敌气味的驱鼠剂 (8-22) · IBM研制新一代芯片可模拟大脑认知能力 (8-22) · 新型显微镜可“看到”活细胞内超微小结构 (8-22) · 英国研究人员发明有触觉的微创手术刀 (8-22) · 杀灭细菌的“生物感应炸弹”问世 (8-22) · 17种新型强效广谱HIV抗体闪亮登场 (8-22) · 注塑技术助力芯片实验室促生命科学大发展 (8-22) · 合成皮肤可替人体软组织有望引领整容新时代 (8-22) · 巨噬细胞可作大脑“清洁工” (8-22) · 世界级美女科学家连发Nature，EMBO Rep文章 (8-19) · 2篇Nature文章：癌症基因组学研究新成果 (8-19) · 罗氏454测序系统新近解读大西洋鳕鱼基因组 (8-19) · 海怪子宫中有个小家伙 (8-19) · 基因流动可帮助作物适应气候变化 (8-19) · 新方法可快速廉价诊断肺结核 (8-19) · 阿司匹林无益于试管授精成功率 (8-19) · 孤独症患者胞弟或胞妹再患此症风险高 (8-19) · 英发现神经细胞中风期间自保机制 (8-19) · 拉什大学研究学者发现或可帮助早期诊断卵巢癌的抗体 (8-19) · F1000：最值得关注的分子生物学论文 (8-18) · Science新周刊两篇文章解析新药效 (8-18) · 用于严重慢性痛风的药物与症状的改善有关 (8-18) · 人参提取物可辅助癌症治疗 (8-18) · 一种蛋白可控制人体脂肪与血糖含量 (8-18) · 研究发现男女自尊心差异不大 (8-18) · 体型小乌贼用“卑鄙”伎俩求爱 (8-18) · 蝴蝶拟态功能由超级基因簇决定 (8-18) · 植物根系与土壤细菌有“地下交易” (8-18) · 康涅狄格大学科学家培育不育的入侵植物新品种 (8-18) · Science、Cell子刊两篇文章聚焦前列腺癌 (8-17) · 干细胞鼻祖Nature子刊破除胚胎干细胞致癌性 (8-17) · 国际组织对能适应极端条件的拟南芥基因组进行测序 (8-17) · 科学家称人脑进化已达极限未来或将萎缩 (8-17) · 氢被发现是热液喷孔生物共生体系的又一能量来源 (8-17) · 牙釉质形成的关键蛋白亮相 (8-17) · 摄取盐分过多导致高血压有内因 (8-17) · 美发现夜盲症基因的重要作用 (8-17)

个人分类: 热点前沿|1563 次阅读|0 个评论

转折正在开始

kejidaobao 2011-6-2 15:43

文/杨书卷 5月中旬，被称为“中国第一部直面艾滋病”的影片《最爱》正在各大影院上映，故事聚焦的艾滋病患者生活在这一随时可能死亡的“末世诅咒”中，与外界隔绝的同时与希望隔绝，所展现的“一个撕裂的世界和无处躲藏的痛苦”，令人身同亲受，潸然泪下。而一份刚刚发布的中国卫生部疫情报告更加重了这种沉重的情绪：2010年全国报告艾滋病发病15982例，死亡7743例，在法定报告传染病中名列第一，从2008年开始，艾滋病死亡病例已连续3年居于传染病死亡的“第一凶手”（5月16日中国新闻网）。值得注意的是，全球大约有6000万的艾滋病感染者，中国还远非艾滋病的“重灾区”。在全世界的注视目光中，有关艾滋病研究的每一步进展都会引发震动。美国研究人员在5月出版的Nature杂志发表报告称，一种试验性疫苗可以帮助携带一种“艾滋病病毒”的猴子在1年多的时间里控制感染。更令人激动的是，论文作者之一、美国俄勒冈全国灵长目研究中心的Luis Pickel博士认为，用于人类试验的疫苗有可能在3年内问世。虽然研制安全、有效的疫苗是控制艾滋病传播的最佳手段之一，但由于艾滋病病毒的“超级”变异性，艾滋病疫苗的研制道路异常艰难，经历无数次失败后，在2008年时甚至有一些艾滋病研究的顶级专家发出了“永远无法研制出艾滋病疫苗”的悲观言论，放弃了用疫苗控制艾滋病毒的想法。有幸的是，从这一实验结果看来，这种言论可能只是科学家精疲力竭的“一时感慨”而非真正的“有效结论”，艾滋病疫苗的研制正在重新回到议程中来。其实，让科学家们屡屡“撞上南墙”的疫苗失败实验中，已经埋下了转变艾滋病病毒疫苗的研究方向的“希望种子”。此次实验的不同之处就在于，利用注射一种改良的“细胞巨化病毒”，就能使免疫系统始终对艾滋病毒保持警惕，即用一种危害并不强烈的病毒阻止一种致命的病毒。在实验中，研究人员给感染“艾滋”的恒河猴注射不同版本的疫苗，超过半数接受治疗的恒河猴体内的猴艾滋病毒消失，该发现显示，这种疫苗能彻底清除体内的艾滋病毒，而传统的抗病毒治疗也能控制艾滋病毒感染，但却无法清除隐藏在免疫系统的白细胞的隐藏区里的病毒。 “这是第一次有一种疫苗能完全控制一些动物体内的病毒。”面对这一艾滋疫苗研制的“转折点”，国际艾滋病疫苗倡议组织首席科学官Wayne Cove博士兴奋不已，“疫苗发展的下一步是在人类的临床实验。作为人类疫苗，细胞巨化病毒的应该更加优秀改良，令其在不会引发疾病的同时，能够有效防御艾滋病毒。”（5月13日《参考消息》）除了艾滋病疫苗的研制，研究人员还在寻求多种全新的方式来彻底消灭这种致命感染。一项由多国科学家参与的研究就发现，艾滋病病毒感染者如果在患病初期就接受抗逆转录病毒（ARV）治疗，则将病毒传染给性伴侣的几率可以减少96%。美国国家过敏与传染病研究所所长Anthony Fauci表示，这一“巨大数字”的研究结果对艾滋病治疗政策的制定有着重要的指导意义，同时“再一次凸显了艾滋病早期治疗的多重含义”（5月18日《科学时报》）。不仅仅在医疗领域，在茫茫宇宙中寻找外星人的行动，也出现了新的方式。如果成功，很有可能成为“世纪大发现”的转折点。在地球上寻找外星人，其实就是寻找太空中可能发来的讯号。现代第一个寻找地外文明的计划是奥兹玛计划，它始于1960年，最初只有一个频道监听外太空信号。现在，世界上最先进的无线电射电望远镜——格林班克100米口径射电望远镜在美国投入搜索，被用来寻找可能存在的“外星人之家”。技术发展到现在，格林班克望远镜的灵敏度绝非同日而语，这座43层楼房高、圆盘大于足球场的“巨镜”，其处理数据量已达到每秒1G的天文数字。这样的计算速度，普通的大型计算机都无法承受。不过，借助互联网的聚合力量，美国科学家想出了最“流行”的方式——号召全球网友参与搜寻外星人讯号，即发动全世界100万个天文爱好者在家处理这些数据。曾是遥不可及的科学家的课题，变为全球天文爱好者的梦想聚集地！只要你愿意，就可以到 http://setiathome.ssl.berkeley.edu 登录注册，分配一个端口进行运算。中国科学院紫金山天文台研究员王思潮呼吁世界网民数量最多的中国网友，也加入到这一激动人心的搜寻队伍中来（5月19日中国新闻网）。有时候，行星也会来个“不按牌理出牌”的“转折”行为。美国西北大学的天文学家Frederick Laxiao及其同事在5月10日出版的Nature杂志撰文称，在系外恒星周围发现的500多颗行星中，大部分行星的公转方向都与恒星的自转方向相同，但一些系外行星却是“反向旋转”的古怪行星，通常是被称作“热木星”的气态巨星。Laxiao对此深感奇怪：“怎么可能恒星朝一个方向旋转，而距离如此之近的行星却朝另一个方向公转？这显然违反了我们对行星和恒星结构的基本认识。”而他们研究后对此的解释是，当行星系统内包含有一颗以上的行星时，除了恒星外,每颗行星也会产生自己的万有引力，导致行星间的相互作用,并最终将一些气态巨星拉向恒星，甚至改变它的运行轨道，成为“反向”行星，这一研究加深了我们对宇宙的多层次认知。在科学中，转折即意味着改变，迥异常规的出击是一种智力挑战，也总是带来新的希望。但是在某些领域，如对抗艾滋病的战争中，最好的办法仍然是预防，从开始就阻止它的发生。也许，人类健康的生活方式在治愈旧疾病、抵抗新疾病上，永远是至关重要、不可替代的。■

个人分类: 科技风云|2172 次阅读|0 个评论

口交也要戴套套

热度 1 andrologist 2011-3-5 22:47

口交是指以唇、舌、齿及喉部刺激生殖器的性行为。它正常吗？这点似乎毋需多言，因为大多数性学家认为，在具有完全行为能力的成年人之间发生的、双方均能接受的性行为都是正常的。口交也有风险？当然，各种形式的性行为都有一些问题需要注意，口交也不例外。口交没有怀孕的顾虑，但它也并非是一种绝对安全的性行为。口交与艾滋病口交传播艾滋病的概率虽然较肛交、阴道性交为低，但也不是完全没有传播的可能。根据迄今最为权威性的关于口交传播艾滋病病毒危险性的研究，口交传播艾滋病病毒的危险比专家们预计的要高。美国“疾病控制和预防中心”和“加州大学旧金山分校”的研究人员说，虽然过去有一些关于口交传染性的报告，但是新的诊断试验让他们可以确定感染的时间。为确定感染途径，研究人员花费很多精力，他们利用了医学记录，和这些男人们访谈，并在可能的情况下，和他们的伴侣谈话。虽然许多卫生官员一直怀疑口腔性交有一定的传播艾滋病病毒的危险，但是一些研究人员还是为他们研究结果的重要性而惊讶。 “这比我们以为的要高一些，这可能是和男人发生性关系的男人被感染的重要途径，”加州大学旧金山分校的研究人员Frederick Hecht博士这样说道，“没有保护的肛门性交比前些年少多了，但是没有保护的口腔性交没有出现类似的下降，这可能已经成为艾滋病病毒传播的重要方式。” 英国公共卫生实验室管理署（PHLS）的调查发现，在患艾滋病的人群中，因无防护措施的口交而被传染的比例占8%。而临床病例表明，口对阴茎、口对阴道和口对肛门的性交方式均可能传播艾滋病。也就是说，无论施行口交双方的性别为何，他们都有感染艾滋病的危险。口交是如何传递艾滋病的呢？原来，导致艾滋病的人类免疫缺陷病毒（HIV）存在于病人或携带者的血液、精液、精前液及阴道分泌物中，如果施行口交者的口腔或喉咙里有小伤口或溃疡，HIV就能够通过体液与血液的接触而进行传播。因此，这意味着把伴侣的性分泌物吸进口腔可以具有感染艾滋病病毒的危险。如果其中一方已经感染了其它性传播疾病（STDs），传播HIV的几率也会增加。口交与口腔癌经常口交，除了会增加感染性病的风险外，还可诱发头颈癌包括口腔癌和舌癌的发生。美国科学家研究发现，已有强有力的证据表明口交和癌症的联系，在美国，64%的口腔、头部和颈部的癌症是由人类乳头状瘤病毒(Human Papillomavirus，简称HPV)引起的，这种病毒往往通过口交方式传播。口交的次数越多、进行口交的伴侣越多，发生这种致命癌症的可能性就越大。科学家表示，在美国，由乳头状瘤病毒传染而引起的口腔癌症变得越来越普遍，甚至比烟草所引起的还要多。而在世界其它地区，烟草所引起的这类癌症的仍是罪魁祸首。美国俄亥俄州立大学教授茂拉．吉里森博士(Dr. Maura Gillison)在一次科学会议上指出：“跟六个或以上的性伴侣长期进行口交的人，(罹患口腔癌的机率)要比从不口交者高八倍。”这个消息可能会使那些担忧子女口交的家长们引起警觉。那么，怎样才能有效地规避这些风险呢？答案和肛交及阴道性交一样——戴套吧。口交也要戴套？安全套可谓是人类最伟大的发明之一，在正确使用的前提下，它能够把怀孕和传播性病的几率降到最低。不过，国内了解口交安全套知识的人还比较少，而且在阴道性交时尚有许多人不愿戴套，口交时更是懒得费这个事儿。如果口交发生在彼此充分信任的夫妻之间，戴套可能不是很必要，但如果你想找点刺激，那么套套就是不可或缺的了。对男性的口交可以使用普通安全套，不过它们通常会在嘴里留下一股乳胶味，而且上面涂的润滑剂在口交时没什么用，因此许多安全套生产商都推出了口交专用安全套。这种安全套通常使用超薄设计，大多数不添加润滑剂，安全套头部也少了储精囊，有的还会添加各种食用香精如草莓、香蕉、葡萄、巧克力……使得它们尝起来有多种口味。不过，有些安全套附赠的“风味”仅仅是厂家的促销措施，因此在选购的时候，一定要预先读说明书，弄清楚这种安全套用于口交是否合适。那么，对女性的口交有什么保险措施吗？答案是“口交保险膜”（dental dam for oral sex）——它是一张隔在舌头和生殖器之间的乳胶膜，来源于牙科用的阻隔膜（dental dam）。用一个普通的避孕套可以自制简易的口交保险膜——把套套的头部剪掉，再把侧面剪开，让它变成一张长方形的乳胶膜就行了。除去用这种方法自制保险膜之外，在市场上也可以买到专用的口交保险膜，不用说，它们也有着丰富多样的口味，供大家“各取所好”。口交保险膜的制作 What is the best protection for oral sex? Q What is the best type of protection for oral sex? I know that with a guy there are condoms over the counter, but is there any option like for a girl? A There are options available for girls when it comes to oral sex. The whole idea is to keep a barrier between yourself and your partner. When oral sex is performed on a girl, a dental dam can be used. A dental dam is a piece of latex that is placed over the genital before oral sex. This makes a barrier between a person’s mouth and the genitals of the female. If you do not have a dental dam you can make one – it’s very easy! All you need is a pair of scissors, a male condom and about 30 seconds. Here is how you do it: The square piece of latex from the male condom can then be used to place over the female genital before oral sex. For more information on dental dams, visit the website Sexualityandu.ca (www.sexualityandu.ca). Select the sexuality transmitted infections link and then dental dams. If you have any other questions, or would like to discuss your question further, please e-mail again. If you would like to talk, or make an appointment to see a health nurse, just give us a call at 519.482.3416 or 1.877.837.6143.

个人分类: 男性|16762 次阅读|1 个评论

[转载]国家传染病诊断试剂与疫苗工程技术研究中心(厦门大学)

nooney1986 2011-1-25 12:52

在厦门大学校园里，有一幢不起眼的三层小楼，白墙明窗，绿树拥簇。就是这样一栋小楼，近几年却吸引了世人越来越多的目光：这里研制出甲型H1N1流感病毒快速检测试剂，检出本次甲型H1N1流感流行病毒株的灵敏度比普通快速检测试剂高10至100倍；这里研制出国内唯一能完全满足艾滋病病毒抗体诊断试剂盒生产要求的艾滋病病毒重组抗原，在2001年获国家科技进步二等奖；这里还是我国“传染病诊断试剂产业技术创新战略联盟”的牵头单位，成功研制出世界首个基因工程戊肝疫苗等一系列具有自主知识产权新药品种，其中“戊型肝炎病毒免疫优势构象性抗原决定簇的发现及其在诊断中的应用”项目获得2010年度国家技术发明奖二等奖…… 这就是以夏宁邵教授为主任的厦门大学国家传染病诊断试剂与疫苗工程技术研究中心。中心刚成立５年，到底靠什么取得这样的辉煌成绩？日前，记者走进这个中心，走近这群奋战在传染病疫情和突发公共卫生事件一线的科研人员。　　不畏急难险重——研发快速诊断甲流试剂　　讲到奋战在传染病疫情和突发公共卫生事件一线的事情，中心的科研人员首先回忆起甲流快速诊断试剂盒的研制过程。 2009年春季，甲型H1N1流感病毒在墨西哥被发现，随后迅速在全球蔓延。由于病毒的高传染性，有效确诊甲流患者便成为防治甲流的第一道防线。病毒暴发之初，是用PCR仪进行检测，但用这种方法检测，确诊一名甲型H1N1流感患者至少需要一天时间，而且每天只能做几十份的标本，检测成本很高。“必须迅速研发出无需特殊仪器设备便能现场快速诊断的试剂！”中心科研人员决定立即启动甲型H1N1流感现场快速检测试剂研发。“当时，中心所有的事情都让位于甲流快速诊断试剂盒的研制。”中心副主任张军说，“任务不分你我，大家争着抢着上；工作不分昼夜，每天夜深人静的时候，中心实验室里还是灯火通明。2009年5月9日，该中心研制的甲型H1N1流感快速检测试剂经香港大学对美国标本的测定，证实该试剂能有效检出本次甲型流感流行株，灵敏度比普通流感快速检测试剂高10至100倍。5月24日起，厦门市将本产品应用于入境人群初筛。短短两个月时间，就从9662例中检出94例阳性，其中15例最终确诊为新型甲型H1N1流感患者，截获率达83.3%，远超全国口岸平均水平。7月，该产品成为科技部、卫生部的推荐产品之一。实际上，这已经不是该中心第一次承担这种“急难险重”任务。自中心成立以来，每次国家在发生重大传染病疫情和突发公共卫生事件时，都能看到该中心研究人员的身影：艾滋病系列诊断试剂、白血病诊断试剂盒、禽流感特异诊断试剂盒、手足口病诊断试剂盒、戊肝病毒系列诊断试剂盒等一个个响亮的成果将这个中心一次次推到公众视线中。据统计，近5年来，该中心已完成各级政府资助科研项目11项，其中国家级和省级重点重大项目6项，先后向企业提供23项诊断试剂盒生产技术，其中10项已获得新药证书或注册证书并商品化，5项已申报注册证书。回顾这些成果的“诞生”，夏宁邵由衷地说：“科研机构必须面向一线，才能清楚地知道社会需要什么，国家需要什么，自身的研究方向在哪里，做出来的成果也才能真正得到人们的认可。” 　　成果高度原创——戊肝疫苗研制世界领先　　打3针疫苗就能预防戊肝，也许在这一两年内将变为现实。这一疫苗的研制者正是厦门大学国家传染病诊断试剂与疫苗工程技术研究中心。戊型肝炎（戊肝）是中老年急性肝炎、孕妇肝炎死亡的最主要原因，国内曾出现千人死亡的局部大流行。2009年我国自主研制的戊肝疫苗成为世界上迄今唯一完成全部临床前和临床研究的戊肝疫苗。更令人自豪的是：该疫苗是我国第一个高度原创性的基因工程病毒疫苗，是我国罕见的拥有核心自主知识产权和高度垄断性的源头创新性生物药物。该疫苗的研制作为科技部评选出的新中国成立以来我国生物医药领域8项代表性成果之一，出现在“辉煌60年”成就展中。2010年8月，国际著名医学期刊《柳叶刀》杂志发表了这一疫苗的三期临床试验结果，该成果的发表，标志着我国在戊肝疫苗研制上的世界领先地位已赢得国际权威认可。戊肝疫苗成功研制的背后是10年辛苦的付出。长期以来，中心全体人员意识到：如果不能自主创新，综合实力就无法体现；科研成果如果没有自主知识产权，就没有强劲的竞争力和发展力。近期，该中心人员已经研制出国内首支宫颈癌疫苗和尖锐湿疣疫苗，其中，宫颈癌疫苗已经进入临床试验。该成果引起了国际关注，世界卫生组织（WHO）已邀请该中心参与国际HPV疫苗相关质量标准及实验室方法标准化的研究。　　善于团队作战——进入突发传染病应急体系　　近年来，因为中心所取得的一系列高显示度科研成果，中心先后获得福建省新长征突击队、福建省和厦门市工人先锋号、福建省五一先锋岗、厦门大学南强集体特等奖等一系列团体荣誉。夏宁邵也被频频推到媒体和公众面前。但每次面对媒体，他说的第一句话都是：“工作是中心全体人员一起做的，要写就写我们这个团队吧。”这不是刻意的低调。在国家传染病诊断试剂与疫苗工程技术研究中心，“心往一处想，劲往一处使”已成该中心鲜明的团队文化。据说，该中心有一条不成文的规定，即考核时，所有的员工不分等级、不按资历、不看论文发表数量，全部一视同仁。标准只有一个：你对中心的贡献有多大，如果贡献大，哪怕你做的只是基础性和服务性工作，也会被评为优秀。对每一位团队成员的尊重换来了团队成员对中心的无私奉献和热爱。“很辛苦，但是很开心”，已在该中心工作了11年的副教授杜海莲这样说。除了“团结”外，“敬业”也是出了名的。据说，中心的战略合作伙伴之一——养生堂有限公司当年在挑选合作伙伴时，有一条标准是“实验室一定要在半夜12点以前不关灯”，最后有人向该公司推荐了这个当年还只是教育部重点实验室下的一个小课题组的团队，几经考察和了解，该公司老总最终下定决心与中心合作，组建“厦门大学养生堂生物药物联合实验室”。实践证明，联合实验室的建立为中心的发展奠定了坚实的基础。谈到成功秘诀，张军表示：“政府和学校的支持、广大协作单位的支撑、团队的高度契合和凝聚力就是我们事业发展的‘制胜法宝’”。中心是一个年轻的团队，拥有145位一线科研人员，平均年龄27.7岁。为了保证团队间合作的紧密性，在人才管理方面坚持“培养为主、引进为辅”和“与团队融合者取，不能者弃”的两条原则。在引进人才时，中心更看重人才与团队的融合度、技术特长以及科研背景，不拘一格引进、提拔、使用人才。厦大打破常规，特许中心全职引进海外著名资深学者融入自身科研团队，2001年邀请加盟的原香港大学微生物学系主任吴文翰教授、2005年邀请加盟的原美国国立卫生研究院临床中心病毒检验室主任史维国教授与中心融为一体，迅速与世界卫生组织、联合国发展署国际疫苗研究所、美国国立卫生研究院（NIH）、英国医学研究中心（MRC）、德国联邦血清与疫苗管理局（PEI）等国际一流研究机构开展了实质性科研合作，创立了中心科研工作及成果的国际化工作中起点高、实效强、战略格局好的有利局面。夏宁邵说：“中心将以高起点的成果转化关键技术平台和源头创新性研究为建设重点，形成从基础和应用基础研究、中试研究、临床试验和成果产业化的完整链条，成为推动我国传染病预防控制产学研核心机构之一，以及我国突发传染病疫情应急体系的组成核心之一。”

个人分类: 生物实验室|2248 次阅读|0 个评论

2011年医学研究热点：白血病骨髓移植的研究动态与文献分析

xupeiyang 2011-1-19 10:39

医学专家预测2011年医学领域可能有的七大进展 http://news.sciencenet.cn/htmlnews/2011/1/243041.shtm 科学家将宣布HIV疫苗研究结果 2010年12月，德国科学家在美国《血液》月刊上发表报告称，他们通过骨髓移植疗法“治愈”了一名艾滋病患者。科学家介绍说，2007年，一名美国男性艾滋病病毒携带者因患白血病在柏林接受骨髓移植治疗，当时捐献者的骨髓配型不仅非常吻合，而且还拥有能天然抵御艾滋病病毒的变异基因Delta 32。3年后，这名美国病人已不再有白血病和艾滋病病毒感染的迹象。 Prediction 2: Results of a promising HIV vaccine will be announced. An American man made international headlines this month when German doctors announced he had been cured of the virus that causes AIDS. The HIV-positive man had suffered from acute myeloid leukemia — a deadly blood cancer — so in 2007 the doctors performed a bone marrow transplant to treat the leukemia. They were lucky enough to find a bone marrow donor with a rare mutation, called Delta 32, that provides natural resistance to the human immunodeficiency virus . http://www.myhealthnewsdaily.com/seven-predicted-medical-advances-in-2011-0949/ http://www.gopubmed.org/web/gopubmed/WEB16OWEB10O0 HIV and leukemia and bone marrow transplant 信息分析报告： HIV and leukemia and bone marrow transplant 1-19.docx

个人分类: 信息分析|2570 次阅读|0 个评论

T细胞阻断艾滋病病毒的信息分析与知识发现

xupeiyang 2010-5-19 13:37

信息分析平台 http://www.gopubmed.org/web/gopubmed/1?WEB0auwa08uox6uiI6I9I00h01000j100200010 543 documents semantically analyzed 1 2 Top Years Publications 1996 34 2008 32 2002 32 1997 32 2007 31 1998 30 2009 28 2006 28 2005 27 2004 27 2003 25 1994 25 1990 25 2000 22 2001 21 1995 19 1993 19 1992 17 1989 17 1999 16 1 2 1 2 Top Countries Publications USA 306 France 30 Italy 27 United Kingdom 22 Netherlands 18 Canada 17 Japan 16 Germany 15 Spain 11 Australia 11 Switzerland 10 Belgium 7 Austria 4 Norway 3 India 3 Taiwan 3 China 2 Macedonia 2 Israel 2 Denmark 2 1 2 1 2 3 ... 8 Top Cities Publications Bethesda 42 New York 37 Boston 22 Philadelphia 20 Baltimore 20 San Francisco 20 Paris 18 Amsterdam 12 London 12 Rome 11 Frederick 7 Milan 7 Seattle 7 Birmingham, USA 5 Nashville 5 Leuven 5 Madrid 4 Badalona 4 Atlanta 4 Chicago 4 1 2 3 ... 8 1 2 3 ... 9 Top Journals Publications J Virol 93 Virology 34 J Immunol 30 Aids Res Hum Retrov 27 P Natl Acad Sci Usa 17 J Biol Chem 14 Aids 13 Nature 10 J Exp Med 10 Blood 9 Gene Ther 9 J Clin Invest 9 J Gen Virol 8 Science 7 Cell Immunol 7 Plos Pathog 6 Eur J Immunol 6 Antimicrob Agents Ch 6 Plos One 5 Nat Med 5 1 2 3 ... 9 1 2 3 ... 135 Top Authors Publications Gallo R 9 Sattentau Q 6 Levy J 6 Moore J 6 Clapham P 6 Knight S 6 Patterson S 6 Clotet B 5 Blauvelt A 5 Steinman R 5 Lusso P 5 Schols D 5 Pomerantz R 5 Offord R 5 Littman D 5 Ensoli B 5 Volsky D 5 Weiss R 5 Paxton W 4 Hartley O 4 1 2 3 ... 135 1 2 3 ... 165 Top Terms Publications Humans 497 HIV 448 T-Lymphocytes 445 Viruses 445 HIV-1 409 T-cell surface glycoprotein CD4 297 HIV Infections 245 Virus Replication 215 Proteins 212 Cell Line 197 CD4-Positive T-Lymphocytes 173 Lymphocytes 170 Animals 168 Antibodies 151 antigen binding 150 viral genome replication 128 Cells, Cultured 116 Acquired Immunodeficiency Syndrome 111 Antigens, CD4 110 Immunization 109 1 2 3 ... 165 知识发现平台 http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi Start A-Literature C-Literature B-list Filter Literature A-query: T-Cells and Block and HIV C-query: cancer cells and viruses The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 46 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 3409 and can be accessed from the start page after you leave this session. There are 835 terms on the current B-list ( 355 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. Rank Prob B-term 10.98highly active antiretroviral 20.98lentiviral vector 30.98v3 loop 40.98antiretroviral therapy 50.98zinc finger 60.98resistant human immunodeficiency 70.98monocyte derived dendritic 80.98cd4 binding 90.98t tropic 100.98transmission hiv-1 110.98hiv-1-infected 120.98retroviral mediated gene 130.98siv specific 140.97retroviral mediated 150.97hiv-1 long terminal 160.97hiv specific 170.97siv specific cd4 180.97expression rna interference 190.97hiv-1 transmission 200.97course hiv-1 210.97conditionally replicating 220.97coreceptor expression 230.97kappab activation 240.97regulatory t cell 250.97nf kappab activation 260.97v3-specific 270.96immunodeficiency virus variant 280.96transmission hiv 290.96immunodeficiency virus 1-infected 300.96human t lymphotropic 310.96loop human immunodeficiency 320.96t lymphotropic 330.96transmission human immunodeficiency 340.96productive human immunodeficiency 350.96v3 loop human 360.96activation human immunodeficiency 370.96jurkat t 380.96hiv-1 infected 390.96nf kappa 400.96siv infected 410.96anti retroviral 420.96hiv-1 fusion 430.96infected macaque 440.96env 450.96therapy hiv 460.96cell cycle arrest 470.96specific cd8 480.96infected human immunodeficiency 490.96derived dendritic 500.96highly active 510.96transcriptional regulation 520.96t cell activation 530.96dc signr 540.96nf kappab 550.96cd8 t 560.96infection human dendritic 570.95zinc finger transcription 580.95viral burden 590.95hiv-1 variant 600.95cell retroviral 610.95cd4-induced 620.95hiv-1 strain 630.95factor kappa b 640.95hiv-1 infectivity 650.95nuclear factor kappa 660.95region human immunodeficiency 670.95hiv therapy 680.95t cell line 690.95expression cd4 700.95complex class i 710.95immature dendritic cell 720.95infected simian immunodeficiency 730.95expression apoptosis 740.94b cell line 750.94hiv-1 expression 760.94hiv-1-specific 770.94virus specific cd8 780.94specific cd4 790.94expression human immunodeficiency 800.94primary hiv-1 810.94depletion human immunodeficiency 820.94cxcr4 expression 830.94histocompatibility complex class 840.94naive t 850.94viral long terminal 860.94immunodeficiency virus infected 870.941-infected 880.94vaccine vector 890.94specific cytotoxic t 900.94cd4 t 910.94nuclear localization 920.94specific cd4 t 930.94transgenic mouse model 940.93human cd4 t 950.93antigen specific t 960.93activated t 970.93cloning expression 980.93virus 1-infected 990.93kappa b 1000.93hiv variant 1010.93neutralization human immunodeficiency 1020.93hiv infected 1030.93gp120-binding 1040.93siv infected macaque 1050.93gag pol 1060.93replication competent 1070.93rna binding 1080.93retroviral 1090.93t cell proliferation 1100.92hiv env 1110.92ankyrin repeat 1120.92cd4-expressing 1130.92specific t cell 1140.92immunodeficiency virus type-1 1150.92immunodeficiency virus transmission 1160.92virus based vector 1170.92novel hiv 1180.92virus specific t 1190.92infected human t 1200.92kappa b activation 1210.92viral cellular gene 1220.92terminal domain 1230.92mechanism cd4 1240.92mature dendritic cell 1250.92progression hiv 1260.92cell cycle progression 1270.91hiv infected patient 1280.91human hematopoietic 1290.91expression hiv-1 1300.91restriction hiv-1 1310.91binding hiv-1 1320.91structure hiv-1 1330.91natural killer 1340.91productive infection 1350.91virus t 1360.91mannose binding 1370.91nef function 1380.91macrophage inflammatory 1390.90increase hiv-1 1400.90transfer hiv-1 1410.90immunodeficiency virus strain 1420.90stage human immunodeficiency 1430.90expression t cell 1440.90hiv-1 seropositive 1450.90replication chronically infected 1460.90function dendritic cell 1470.90virus life cycle 1480.90fusion protein human 1490.90hiv-1 viral 1500.89latently infected 1510.89retention signal 1520.89packaging signal 1530.89replication latently infected 1540.89latently 1550.89soluble cd4-induced 1560.89cell mediated transmission 1570.89necrosis factor alpha 1580.89viral entry 1590.89treatment hiv 1600.89constitutive expression 1610.89stably expressing 1620.88hiv-1 subtype 1630.88gp120 binding 1640.88cellular cytotoxicity 1650.88hiv-1 restriction 1660.88tropic strain 1670.88persistently infected 1680.88primary t cell 1690.88retroviral infection 1700.88model hiv-1 infection 1710.88cd4 expression 1720.87human hematopoietic cell 1730.87productive hiv infection 1740.87chronically infected cell 1750.87specific t 1760.87multiple immunodominant 1770.87cell hiv infected 1780.87human dendritic 1790.87primary hiv-1 isolate 1800.86macrophage tropic strain 1810.86viral replication 1820.86treatment hiv infection 1830.86interview mark mascolini 1840.86region cd4 1850.86hiv infected individual 1860.85specific cytotoxic 1870.85peripheral blood t 1880.85t cell subset 1890.85gp120 viral 1900.85infection fusion 1910.85novel cationic 1920.85hematopoietic cell line 1930.85transfer cd4 1940.85expression hiv 1950.85virus type-1 1960.85ctl line 1970.85decay accelerating factor 1980.85effector t cell 1990.84inhibit viral 2000.84domain fusion protein 2010.84restriction factor trim5alpha 2020.84macrophage t 2030.84ccr5 expression 2040.83gene transfer 2050.83epithelial cell line 2060.83viral cellular 2070.83autocrine loop 2080.83expression peripheral blood 2090.82infection primary human 2100.82early hiv-1 infection 2110.82human placental trophoblast 2120.82virus binding 2130.82nf 2140.82virus 1-induced 2150.82cell activation 2160.81calmodulin binding 2170.81interferon treatment 2180.81effect hiv 2190.81virus specific 2200.81virus productive 2210.81expression stromal 2220.81infection human t 2230.81proviral expression 2240.81major histocompatibility 2250.81alpha induced 2260.81stably 2270.81expression rna 2280.80advanced human immunodeficiency 2290.80cell binding 2300.80control hiv 2310.80autologous cd4 2320.80hiv strain 2330.79virus infection fusion 2340.79activation th1 2350.79persistently infected human 2360.79c terminal domain 2370.79neutralization human 2380.79identification novel 2390.79level hiv-1 2400.78virus dendritic 2410.78constitutive expression hiv-1 2420.78infected simian 2430.78placental trophoblast 2440.78primary macrophage 2450.78level soluble tumor 2460.77defective hiv-1 2470.77site human immunodeficiency 2480.77simplex virus 1-induced 2490.77hiv-1 infection primary 2500.77macrophage culture 2510.76adenosine deaminase binding 2520.76peripheral blood monocyte 2530.76progressor 2540.76immunodeficiency virus production 2550.76function chemokine receptor 2560.76virus type-1 tat 2570.76virus infected cell 2580.751-induced 2590.75humoral cellular 2600.75virus hiv infected 2610.75infected individual 2620.75neutralization 2630.75surrogate marker 2640.75binding lectin 2650.74pol 2660.74class hiv 2670.74virus variant 2680.74b activation 2690.74type-1 tat protein 2700.74hiv-1 production 2710.74chemotherapy 2720.73lymphoid cell line 2730.73expression virus 2740.73infection human cervical 2750.73enhance viral 2760.73infected cell line 2770.72human cervical 2780.72membrane binding 2790.72control viral replication 2800.72activation induced 2810.72hiv infected cell 2820.72proliferative response 2830.71cell infected 2840.71rna expression 2850.71hematopoietic cell 2860.71virological synapse 2870.71suppression siv specific 2880.71binding hiv-1 gp120 2890.71strain human immunodeficiency 2900.70region human 2910.70virus production 2920.70presentation t cell 2930.70ccr5-expressing 2940.70inhibition viral 2950.69virus strain 2960.69membrane proximal 2970.69primary endocervical 2980.68pathogenesis a novel 2990.68restrict hiv-1 infection 3000.68lymphocyte function associated 3010.68stage hiv disease 3020.68infection peripheral 3030.68infected cell 3040.67expression a 3050.67site hiv-1 3060.66hematopoietic 3070.66genital tract 3080.66infection potential therapeutic 3090.66vaccine immunogenicity protective 3100.65expression transfected 3110.65hiv-1-induced 3120.65associated viral 3130.65mechanism hiv 3140.65virus neutralization 3150.65expression human 3160.65chronically infected 3170.65cell line primary 3180.65site human 3190.65mouse model 3200.65chronically infected human 3210.65histocompatibility 3220.65specific gamma interferon 3230.64coreceptor function 3240.64function human immunodeficiency 3250.64infected patient 3260.64virus challenge 3270.64cell specific 3280.64repeat 3290.63viral particle 3300.63antiviral property 3310.63primary dendritic cell 3320.63amino terminal 3330.63lymphocyte function 3340.63human t 3350.62n terminus 3360.61factor alpha 3370.60infected human 3380.60expression primary 3390.60primary human lymphocyte 3400.60t cell dendritic 3410.59vector 3420.59dendritic 3430.58type-1 3440.58benefit hiv 3450.58protect human hematopoietic 3460.58high efficiency 3470.57conditionally 3480.57virus infected individual 3490.57class i 3500.57expression cd4 receptor 3510.57cell line infected 3520.57vesicular 3530.56lymphocytic 3540.56kappa 3550.54virus transmission 3560.54synthesis biological 3570.54autologous 3580.53role viral 3590.53c terminal 3600.53potently 3610.52c terminus 3620.52effect t cell 3630.52female genital 3640.51infected endothelial cell 3650.51infected children 3660.51cell persistently infected 3670.51immunogenicity a 3680.51immunogenicity 3690.51vaccination protocol 3700.50stably express 3710.49virus entry t 3720.49infection t 3730.49virus replication cycle 3740.49control hiv infection 3750.49trophoblast culture 3760.49persistently 3770.48induce t 3780.48virus model 3790.48vitro model 3800.48control viral 3810.48novel hiv-1 3820.47viral transmission 3830.47differentially 3840.47infection primary 3850.47novel human immunodeficiency 3860.47allele specific 3870.47virus hiv-1 infected 3880.46t cell primary 3890.45anti viral 3900.45productive 3910.44suppressor 3920.44vaccine immunogenicity 3930.43cd4 primary 3940.42amino terminal domain 3950.42cell dysfunction 3960.42placental cell 3970.42cytotoxic function 3980.41infected primary 3990.41genital 4000.40vertically 4010.40positive cell 4020.40latency 4030.40abortively infected 4040.40infectivity 4050.40restriction 4060.40cervical tissue 4070.40activator 4080.40activation simian 4090.38functional analysis 4100.38seronegative 4110.38dc 4120.38potent inhibitor 4130.38inflammatory protein 1alpha 4140.37initiation 4150.37dendritic cell t 4160.36cell free 4170.36therapeutic potential 4180.36virus infected children 4190.36cervical 4200.36topical microbicide 4210.36model studying 4220.36competent 4230.36high risk 4240.35suppressive 4250.35cellular response 4260.35virus infected 4270.33epithelial 4280.33arrest 4290.33sufficient 4300.32effector 4310.32binding cell 4320.32effect glucocorticoid 4330.31display 4340.30regulatory 4350.30t lymphocyte surface 4360.29infectability 4370.29seropositive 4380.29t cell peripheral 4390.29fusion 4400.28|--fusion cell 4410.28stage virus 4420.27life cycle 4430.27viral 4440.27molecular mechanism 4450.26proliferation 4460.26binding t cell 4470.26dissemination 4480.25cell transfer 4490.25monocytic 4500.25loop 4510.24independently 4520.23specific inhibition 4530.23conformational 4540.22novel approach 4550.22bipartite 4560.22resistant 4570.22immunogenicity protective efficacy 4580.22survival 4590.22activation signal 4600.22virus increase 4610.21mucosal 4620.21peripheral blood leukocyte 4630.21immune 4640.20defective 4650.20rectal 4660.20binding human 4670.20function human 4680.20cultured vitro 4690.20cultured human 4700.19humoral 4710.19function cd4 4720.19nuclear 4730.19immune mechanism 4740.18terminally 4750.18establishment 4760.17susceptibility 4770.17virological 4780.17cell derived factor 4790.17therapeutic strategy 4800.16directly 4810.16inhibited 4820.16separable 4830.16immunology 4840.16aberrant 4850.16progression 4860.16specific binding 4870.16potent 4880.15conformation 4890.15variant 4900.15intracellular 4910.15effect chemotherapy 4920.15lymphocytic cell line 4930.15mature 4940.15acutely infected 4950.15homologous viral 4960.15line peripheral blood 4970.15safety immunogenicity 4980.14inhibitory effect 4990.14core 5000.14t lymphocyte cell 5010.14potency 5020.14latent 5030.14therapeutic target 5040.14combination 5050.14cell line peripheral 5060.13evaluation anti 5070.13expression 5080.13genetic 5090.13highly potent 5100.13therapeutic index 5110.13disruption 5120.13differentiation 5130.13species specific 5140.12signal 5150.12binding 5160.12cycle 5170.12immediate 5180.12terminal 5190.11class 5200.11full 5210.11variant associated 5220.10line 5230.10depletion 5240.102-induced 5250.10marker 5260.10multiplication 5270.10potential therapeutic 5280.10c c 5290.10repeat protein 5300.09green 5310.09highly 5320.09long lasting 5330.09marked 5340.09extracellular 5350.09site 5360.08homologous 5370.08predisposition 5380.08cell early 5390.08novel 5400.08cell application 5410.08cell a new 5420.07proliferative 5430.07region 5440.07infected 5450.07infectivity not 5460.07cellular 5470.07regulation virus 5480.07cell primary 5490.07human placental 5500.07efficiency 5510.07activation 5520.06transfer 5530.06advanced 5540.06salivary 5550.06growth 5560.06modulation 5570.05channel 5580.05potent specific 5590.05regulation 5600.05potential 5610.05broad 5620.05endogenous 5630.05circular 5640.05expansion 5650.05infected monkey 5660.05augmentation 5670.04isolated peripheral blood 5680.04generation 5690.04pathogenicity 5700.04spread 5710.04protein bound 5720.04treat 5730.04cell early stage 5740.04peripheral 5750.04complex 5760.04infected cultured human 5770.04natural 5780.04surrogate 5790.04effective 5800.04increase 5810.04major 5820.04sensitivity 5830.04low molecular 5840.04chronically 5850.04sensitive 5860.04circle 5870.04coat 5880.04fungal 5890.04pore 5900.03positive 5910.03specific 5920.03persistent 5930.03synthesis novel 5940.03mechanistic 5950.03production 5960.03presentation 5970.03differential 5980.03inversely 5990.03alpha 6000.03isolation characterization 6010.03surface 6020.03model 6030.03chronic progressive 6040.03residue 6050.03discontinuous 6060.03multiple 6070.03beta 6080.03long 6090.03primary 6100.03potential role 6110.03domestic 6120.03therapeutic application 6130.02increased 6140.02culture 6150.02functional 6160.02immature 6170.02single 6180.02early stage 6190.02therapeutic 6200.02transmission 6210.02cell stably 6220.02therapy 6230.02protocol 6240.02clinical trial 6250.02humoral response 6260.02vaginal 6270.02positive negative 6280.02mitochondrial 6290.01pathogenesis 6300.01small 6310.01cell new 6320.01placental 6330.01low dose 6340.01cultured 6350.01mechanism 6360.01prophylaxis 6370.01acutely 6380.01cost 6390.01late 6400.01low level 6410.01active 6420.01topical 6430.01high 6440.01lack 6450.01alteration 6460.01localization 6470.01virus release 6480.01new viral 6490.01differential effect 6500.01stabilization 6510.01molecular weight 6520.01balance 6530.01direct 6540.01weight 6550.01pathogenic 6560.01cutaneous 6570.01early 6580.01suppressive effect 6590.00quality 6600.00poor 6610.00penetration 6620.00subtype 6630.00treatment regimen 6640.00serum level 6650.00longitudinal 6660.00phase 6670.00stability 6680.00neuronal 6690.00risk 6700.00structural 6710.00human cervical tissue 6720.00confirmation 6730.00neural 6740.00disease model 6750.00refractory 6760.00intrinsic 6770.00function 6780.00inflammatory 6790.00structure 6800.00deposition 6810.00stage infection 6820.00progressive 6830.00threshold 6840.00rapidly 6850.00residual 6860.00decrease 6870.00failure 6880.00prerequisite 6890.00capacity 6900.00cell intracellular 6910.00pd 6920.00extent 6930.00possible mechanism 6940.00segment 6950.00rapid 6960.00clear 6970.00benefit 6980.00systematic 6990.00index 7000.00virus genetic 7010.00bacterial 7020.00strain 7030.00extensive 7040.00migratory 7050.00variable 7060.00stage 7070.00isolation 7080.00acquired 7090.00onset 7100.00greater 7110.00proximal 7120.00cardiovascular 7130.00proliferation infection 7140.00virus a model 7150.00physical 7160.00separate 7170.00cell rapid 7180.00newly 7190.00intermediate 7200.00dependence 7210.00therapeutic activity 7220.00reactivity 7230.00availability 7240.00cell course 7250.00scenario 7260.00retention 7270.00mechanism action 7280.00kinetic 7290.00prior 7300.00dead end 7310.00defect 7320.00life 7330.00demonstration 7340.00species 7350.00population 7360.00end 7370.00release 7380.00dose 7390.00long term 7400.00organization 7410.00involvement 7420.00exposure 7430.00basic 7440.00self 7450.00activation growth 7460.00dysfunction 7470.00affecting 7480.00partial 7490.00metabolism 7500.00degree 7510.00isolated 7520.00second 7530.00different 7540.00size 7550.00place 7560.00polar 7570.00common 7580.00growth multiple 7590.00biological 7600.00control infection 7610.00course 7620.00challenge 7630.00origin 7640.00progress 7650.00health 7660.00deficiency 7670.00prolonged 7680.00derivation 7690.00form 7700.00free 7710.00compound 7720.00difference 7730.00chemistry 7740.00iv 7750.00dynamic 7760.00property 7770.00reversal 7780.00acute 7790.00low 7800.00short 7810.00mark 7820.00status 7830.00activation virus 7840.00susceptibility infection 7850.00quantitative 7860.00simple 7870.00first 7880.00action 7890.00concept 7900.00formation 7910.00possible 7920.00post 7930.00virus relationship 7940.00control 7950.00long lived 7960.00approach 7970.00charge 7980.00chronic 7990.00review 8000.00level 8010.00application 8020.00short long term 8030.00functionality 8040.00pattern 8050.00qualitative 8060.00controlled 8070.00new approach 8080.00treatment 8090.00two 8100.00serial 8110.00report 8120.00relationship 8130.00comparison 8140.00evaluation 8150.00clinical 8160.00part 8170.00clinical course 8180.00method 8190.00micro 8200.00inhibition activation 8210.00system 8220.00reality 8230.00prophylaxis therapy 8240.00overview 8250.00need 8260.00effect 8270.00exclusion 8280.00new 8290.00promising new 8300.00vitro effect 8310.00compensation 8320.00effect infection 8330.00new frontier 8340.00organism 8350.00d Restrict by semantic categories? 检索策略 job id # 3409 started Wed May 19 02:11:32 2010 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 3409 Search ARROWSMITH A A_query_raw: T-Cells and Block and HIVWed May 19 02:20:16 2010 A query = T-Cells and Block and HIV started Wed May 19 02:20:16 2010 A query resulted in 543 titles 3409 Search ARROWSMITH C C_query_raw: cancer cells and viruses Wed May 19 02:21:21 2010 C: cancer cells and viruses 19930 A: pubmed_query_A 543 AC: ( T-Cells and Block and HIV ) AND ( cancer cells and viruses ) 46 C query = cancer cells and viruses started Wed May 19 02:21:22 2010 C query resulted in 19930 titles A AND C query resulted in 46 titles 3443 B-terms ready on Wed May 19 02:23:07 2010 Sem_filter: Concepts Ideas 835 B-terms left after filter executed Wed May 19 02:26:10 2010 相关知识概念 Sem_filter: Concepts Ideas 835 B-terms left after filter executed Wed May 19 02:26:10 2010 B-list on Wed May 19 02:27:35 2010 1 highly active antiretroviral 2 lentiviral vector 3 v3 loop 4 antiretroviral therapy通过这个关键词（知识点）发现相关的研究课题（见以下实例） 5 zinc finger 6 resistant human immunodeficiency 7 monocyte derived dendritic 8 cd4 binding 9 t tropic 10 transmission hiv-1 11 hiv-1-infected 12 retroviral mediated gene 13 siv specific 14 retroviral mediated 15 hiv-1 long terminal 16 hiv specific 17 siv specific cd4 18 expression rna interference 19 hiv-1 transmission 20 course hiv-1 21 conditionally replicating 22 coreceptor expression 23 kappab activation 24 regulatory t cell 25 nf kappab activation 26 v3-specific 27 immunodeficiency virus variant 28 transmission hiv 29 immunodeficiency virus 1-infected 30 human t lymphotropic 31 loop human immunodeficiency 32 t lymphotropic 33 transmission human immunodeficiency 34 productive human immunodeficiency 35 v3 loop human 36 activation human immunodeficiency 37 jurkat t 38 hiv-1 infected 39 nf kappa 40 siv infected 41 anti retroviral 42 hiv-1 fusion 43 infected macaque 44 env 45 therapy hiv 46 cell cycle arrest 47 specific cd8 48 infected human immunodeficiency 49 derived dendritic 50 highly active 51 transcriptional regulation 52 t cell activation 53 dc signr 54 nf kappab 55 cd8 t 56 infection human dendritic 57 zinc finger transcription 58 viral burden 59 hiv-1 variant 60 cell retroviral 61 cd4-induced 62 hiv-1 strain 63 factor kappa b 64 hiv-1 infectivity 65 nuclear factor kappa 66 region human immunodeficiency 67 hiv therapy 68 t cell line 69 expression cd4 70 complex class i 71 immature dendritic cell 72 infected simian immunodeficiency 73 expression apoptosis 74 b cell line 75 hiv-1 expression 76 hiv-1-specific 77 virus specific cd8 78 specific cd4 79 expression human immunodeficiency 80 primary hiv-1 81 depletion human immunodeficiency 82 cxcr4 expression 83 histocompatibility complex class 84 naive t 85 viral long terminal 86 immunodeficiency virus infected 87 1-infected 88 vaccine vector 89 specific cytotoxic t 90 cd4 t 91 nuclear localization 92 specific cd4 t 93 transgenic mouse model 94 human cd4 t 95 antigen specific t 96 activated t 97 cloning expression 98 virus 1-infected 99 kappa b 100 hiv variant 101 neutralization human immunodeficiency 102 hiv infected 103 gp120-binding 104 siv infected macaque 105 gag pol 106 replication competent 107 rna binding 108 retroviral 109 t cell proliferation 110 hiv env 111 ankyrin repeat 112 cd4-expressing 113 specific t cell 114 immunodeficiency virus type-1 115 immunodeficiency virus transmission 116 virus based vector 117 novel hiv 118 virus specific t 119 infected human t 120 kappa b activation 121 viral cellular gene 122 terminal domain 123 mechanism cd4 124 mature dendritic cell 125 progression hiv 126 cell cycle progression 127 hiv infected patient 128 human hematopoietic 129 expression hiv-1 130 restriction hiv-1 131 binding hiv-1 132 structure hiv-1 133 natural killer 134 productive infection 135 virus t 136 mannose binding 137 nef function 138 macrophage inflammatory 139 increase hiv-1 140 transfer hiv-1 141 immunodeficiency virus strain 142 stage human immunodeficiency 143 expression t cell 144 hiv-1 seropositive 145 replication chronically infected 146 function dendritic cell 147 virus life cycle 148 fusion protein human 149 hiv-1 viral 150 latently infected 151 retention signal 152 packaging signal 153 replication latently infected 154 latently 155 soluble cd4-induced 156 cell mediated transmission 157 necrosis factor alpha 158 viral entry 159 treatment hiv 160 constitutive expression 161 stably expressing 162 hiv-1 subtype 163 gp120 binding 164 cellular cytotoxicity 165 hiv-1 restriction 166 tropic strain 167 persistently infected 168 primary t cell 169 retroviral infection 170 model hiv-1 infection 171 cd4 expression 172 human hematopoietic cell 173 productive hiv infection 174 chronically infected cell 175 specific t 176 multiple immunodominant 177 cell hiv infected 178 human dendritic 179 primary hiv-1 isolate 180 macrophage tropic strain 181 viral replication 182 treatment hiv infection 183 interview mark mascolini 184 region cd4 185 hiv infected individual 186 specific cytotoxic 187 peripheral blood t 188 t cell subset 189 gp120 viral 190 infection fusion 191 novel cationic 192 hematopoietic cell line 193 transfer cd4 194 expression hiv 195 virus type-1 196 ctl line 197 decay accelerating factor 198 effector t cell 199 inhibit viral 200 domain fusion protein 201 restriction factor trim5alpha 202 macrophage t 203 ccr5 expression 204 gene transfer 205 epithelial cell line 206 viral cellular 207 autocrine loop 208 expression peripheral blood 209 infection primary human 210 early hiv-1 infection 211 human placental trophoblast 212 virus binding 213 nf 214 virus 1-induced 215 cell activation 216 calmodulin binding 217 interferon treatment 218 effect hiv 219 virus specific 220 virus productive 221 expression stromal 222 infection human t 223 proviral expression 224 major histocompatibility 225 alpha induced 226 stably 227 expression rna 228 advanced human immunodeficiency 229 cell binding 230 control hiv 231 autologous cd4 232 hiv strain 233 virus infection fusion 234 activation th1 235 persistently infected human 236 c terminal domain 237 neutralization human 238 identification novel 239 level hiv-1 240 virus dendritic 241 constitutive expression hiv-1 242 infected simian 243 placental trophoblast 244 primary macrophage 245 level soluble tumor 246 defective hiv-1 247 site human immunodeficiency 248 simplex virus 1-induced 249 hiv-1 infection primary 250 macrophage culture 251 adenosine deaminase binding 252 peripheral blood monocyte 253 progressor 254 immunodeficiency virus production 255 function chemokine receptor 256 virus type-1 tat 257 virus infected cell 258 1-induced 259 humoral cellular 260 virus hiv infected 261 infected individual 262 neutralization 263 surrogate marker 264 binding lectin 265 pol 266 class hiv 267 virus variant 268 b activation 269 type-1 tat protein 270 hiv-1 production 271 chemotherapy 272 lymphoid cell line 273 expression virus 274 infection human cervical 275 enhance viral 276 infected cell line 277 human cervical 278 membrane binding 279 control viral replication 280 activation induced 281 hiv infected cell 282 proliferative response 283 cell infected 284 rna expression 285 hematopoietic cell 286 virological synapse 287 suppression siv specific 288 binding hiv-1 gp120 289 strain human immunodeficiency 290 region human 291 virus production 292 presentation t cell 293 ccr5-expressing 294 inhibition viral 295 virus strain 296 membrane proximal 297 primary endocervical 298 pathogenesis a novel 299 restrict hiv-1 infection 300 lymphocyte function associated 301 stage hiv disease 302 infection peripheral 303 infected cell 304 expression a 305 site hiv-1 306 hematopoietic 307 genital tract 308 infection potential therapeutic 309 vaccine immunogenicity protective 310 expression transfected 311 hiv-1-induced 312 associated viral 313 mechanism hiv 314 virus neutralization 315 expression human 316 chronically infected 317 cell line primary 318 site human 319 mouse model 320 chronically infected human 321 histocompatibility 322 specific gamma interferon 323 coreceptor function 324 function human immunodeficiency 325 infected patient 326 virus challenge 327 cell specific 328 repeat 329 viral particle 330 antiviral property 331 primary dendritic cell 332 amino terminal 333 lymphocyte function 334 human t 335 n terminus 336 factor alpha 337 infected human 338 expression primary 339 primary human lymphocyte 340 t cell dendritic 341 vector 342 dendritic 343 type-1 344 benefit hiv 345 protect human hematopoietic 346 high efficiency 347 conditionally 348 virus infected individual 349 class i 350 expression cd4 receptor 351 cell line infected 352 vesicular 353 lymphocytic 354 kappa 355 virus transmission 356 synthesis biological 357 autologous 358 role viral 359 c terminal 360 potently 361 c terminus 362 effect t cell 363 female genital 364 infected endothelial cell 365 infected children 366 cell persistently infected 367 immunogenicity a 368 immunogenicity 369 vaccination protocol 370 stably express 371 virus entry t 372 infection t 373 virus replication cycle 374 control hiv infection 375 trophoblast culture 376 persistently 377 induce t 378 virus model 379 vitro model 380 control viral 381 novel hiv-1 382 viral transmission 383 differentially 384 infection primary 385 novel human immunodeficiency 386 allele specific 387 virus hiv-1 infected 388 t cell primary 389 anti viral 390 productive 391 suppressor 392 vaccine immunogenicity 393 cd4 primary 394 amino terminal domain 395 cell dysfunction 396 placental cell 397 cytotoxic function 398 infected primary 399 genital 400 vertically 401 positive cell 402 latency 403 abortively infected 404 infectivity 405 restriction 406 cervical tissue 407 activator 408 activation simian 409 functional analysis 410 seronegative 411 dc 412 potent inhibitor 413 inflammatory protein 1alpha 414 initiation 415 dendritic cell t 416 cell free 417 therapeutic potential 418 virus infected children 419 cervical 420 topical microbicide 421 model studying 422 competent 423 high risk 424 suppressive 425 cellular response 426 virus infected 427 epithelial 428 arrest 429 sufficient 430 effector 431 binding cell 432 effect glucocorticoid 433 display 434 regulatory 435 t lymphocyte surface 436 infectability 437 seropositive 438 t cell peripheral 439 fusion 440 fusion cell 441 stage virus 442 life cycle 443 viral 444 molecular mechanism 445 proliferation 446 binding t cell 447 dissemination 448 cell transfer 449 monocytic 450 loop 451 independently 452 specific inhibition 453 conformational 454 novel approach 455 bipartite 456 resistant 457 immunogenicity protective efficacy 458 survival 459 activation signal 460 virus increase 461 mucosal 462 peripheral blood leukocyte 463 immune 464 defective 465 rectal 466 binding human 467 function human 468 cultured vitro 469 cultured human 470 humoral 471 function cd4 472 nuclear 473 immune mechanism 474 terminally 475 establishment 476 susceptibility 477 virological 478 cell derived factor 479 therapeutic strategy 480 directly 481 inhibited 482 separable 483 immunology 484 aberrant 485 progression 486 specific binding 487 potent 488 conformation 489 variant 490 intracellular 491 effect chemotherapy 492 lymphocytic cell line 493 mature 494 acutely infected 495 homologous viral 496 line peripheral blood 497 safety immunogenicity 498 inhibitory effect 499 core 500 t lymphocyte cell 501 potency 502 latent 503 therapeutic target 504 combination 505 cell line peripheral 506 evaluation anti 507 expression 508 genetic 509 highly potent 510 therapeutic index 511 disruption 512 differentiation 513 species specific 514 signal 515 binding 516 cycle 517 immediate 518 terminal 519 class 520 full 521 variant associated 522 line 523 depletion 524 2-induced 525 marker 526 multiplication 527 potential therapeutic 528 c c 529 repeat protein 530 green 531 highly 532 long lasting 533 marked 534 extracellular 535 site 536 homologous 537 predisposition 538 cell early 539 novel 540 cell application 541 cell a new 542 proliferative 543 region 544 infected 545 infectivity not 546 cellular 547 regulation virus 548 cell primary 549 human placental 550 efficiency 551 activation 552 transfer 553 advanced 554 salivary 555 growth 556 modulation 557 channel 558 potent specific 559 regulation 560 potential 561 broad 562 endogenous 563 circular 564 expansion 565 infected monkey 566 augmentation 567 isolated peripheral blood 568 generation 569 pathogenicity 570 spread 571 protein bound 572 treat 573 cell early stage 574 peripheral 575 complex 576 infected cultured human 577 natural 578 surrogate 579 effective 580 increase 581 major 582 sensitivity 583 low molecular 584 chronically 585 sensitive 586 circle 587 coat 588 fungal 589 pore 590 positive 591 specific 592 persistent 593 synthesis novel 594 mechanistic 595 production 596 presentation 597 differential 598 inversely 599 alpha 600 isolation characterization 601 surface 602 model 603 chronic progressive 604 residue 605 discontinuous 606 multiple 607 beta 608 long 609 primary 610 potential role 611 domestic 612 therapeutic application 613 increased 614 culture 615 functional 616 immature 617 single 618 early stage 619 therapeutic 620 transmission 621 cell stably 622 therapy 623 protocol 624 clinical trial 625 humoral response 626 vaginal 627 positive negative 628 mitochondrial 629 pathogenesis 630 small 631 cell new 632 placental 633 low dose 634 cultured 635 mechanism 636 prophylaxis 637 acutely 638 cost 639 late 640 low level 641 active 642 topical 643 high 644 lack 645 alteration 646 localization 647 virus release 648 new viral 649 differential effect 650 stabilization 651 molecular weight 652 balance 653 direct 654 weight 655 pathogenic 656 cutaneous 657 early 658 suppressive effect 659 quality 660 poor 661 penetration 662 subtype 663 treatment regimen 664 serum level 665 longitudinal 666 phase 667 stability 668 neuronal 669 risk 670 structural 671 human cervical tissue 672 confirmation 673 neural 674 disease model 675 refractory 676 intrinsic 677 function 678 inflammatory 679 structure 680 deposition 681 stage infection 682 progressive 683 threshold 684 rapidly 685 residual 686 decrease 687 failure 688 prerequisite 689 capacity 690 cell intracellular 691 pd 692 extent 693 possible mechanism 694 segment 695 rapid 696 clear 697 benefit 698 systematic 699 index 700 virus genetic 701 bacterial 702 strain 703 extensive 704 migratory 705 variable 706 stage 707 isolation 708 acquired 709 onset 710 greater 711 proximal 712 cardiovascular 713 proliferation infection 714 virus a model 715 physical 716 separate 717 cell rapid 718 newly 719 intermediate 720 dependence 721 therapeutic activity 722 reactivity 723 availability 724 cell course 725 scenario 726 retention 727 mechanism action 728 kinetic 729 prior 730 dead end 731 defect 732 life 733 demonstration 734 species 735 population 736 end 737 release 738 dose 739 long term 740 organization 741 involvement 742 exposure 743 basic 744 self 745 activation growth 746 dysfunction 747 affecting 748 partial 749 metabolism 750 degree 751 isolated 752 second 753 different 754 size 755 place 756 polar 757 common 758 growth multiple 759 biological 760 control infection 761 course 762 challenge 763 origin 764 progress 765 health 766 deficiency 767 prolonged 768 derivation 769 form 770 free 771 compound 772 difference 773 chemistry 774 iv 775 dynamic 776 property 777 reversal 778 acute 779 low 780 short 781 mark 782 status 783 activation virus 784 susceptibility infection 785 quantitative 786 simple 787 first 788 action 789 concept 790 formation 791 possible 792 post 793 virus relationship 794 control 795 long lived 796 approach 797 charge 798 chronic 799 review 800 level 801 application 802 short long term 803 functionality 804 pattern 805 qualitative 806 controlled 807 new approach 808 treatment 809 two 810 serial 811 report 812 relationship 813 comparison 814 evaluation 815 clinical 816 part 817 clinical course 818 method 819 micro 820 inhibition activation 821 system 822 reality 823 prophylaxis therapy 824 overview 825 need 826 effect 827 exclusion 828 new 829 promising new 830 vitro effect 831 compensation 832 effect infection 833 new frontier 834 organism 835 d 知识发现与相关研究课题实例（AB研究课题与BC研究课题）科研人员通过选择上述有价值的关键词（知识概念）进行检索分析，从中得到科研启发，选择有研究价值的课题 Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature T-Cells and Block and ... antiretroviral therapy cancer cells and viruses 1: Immunophenotypic analyses of CD34(+) cell subsets in bone marrow from HIV-infected patients during highly- active antiretroviral therapy .2002 Add to clipboard 1: Immunologic and virologic predictors of AIDS-related non-hodgkin lymphoma in the highly active antiretroviral therapy era.2010 Add to clipboard 2: Imiquimod 5% cream for external genital or perianal warts in human immunodeficiency virus-positive patients treated with highly active antiretroviral therapy : an open-label, noncomparative study.2009 Add to clipboard 3: Antiretroviral therapy restores diversity in the T-cell receptor Vbeta repertoire of CD4 T-cell subpopulations among human immunodeficiency virus type 1-infected children and adolescents.2009 Add to clipboard 4: Concurrent Chemoradiotherapy with 5-Fluorouracil and Mitomycin C for Invasive Anal Carcinoma in Human Immunodeficiency Virus-Positive Patients Receiving Highly Active Antiretroviral Therapy .2009 Add to clipboard 5: Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study.2009 Add to clipboard 6: Highly active antiretroviral therapy and incidence of cervical squamous intraepithelial lesions among HIV-infected women with normal cytology and CD4 counts above 350 cells/mm3.2008 Add to clipboard 7: Relationship between CD38 expression on peripheral blood T-cells and monocytes, and response to antiretroviral therapy : a one-year longitudinal study of a cohort of chronically infected ART-naive HIV-1+ patients.2007 Add to clipboard 8: Brief report: effectiveness of combination antiretroviral therapy on survival and opportunistic infections in a developing world setting: an observational cohort study.2007 Add to clipboard 9: Immunologic, virologic, and neuropsychologic responses in human immunodeficiency virus-infected children receiving their first highly active antiretroviral therapy regimen.2007 Add to clipboard 10: Human papillomavirus type 26 infection causing multiple invasive squamous cell carcinomas of the fingernails in an AIDS patient under highly active antiretroviral therapy .2007 Add to clipboard 11: Interferon-alpha2b with protease inhibitor-based antiretroviral therapy in patients with AIDS-associated Kaposi sarcoma: an AIDS malignancy consortium phase I trial.2006 Add to clipboard 12: Persistent abnormalities in peripheral blood dendritic cells and monocytes from HIV-1-positive patients after 1 year of antiretroviral therapy .2006 Add to clipboard 13: Ceramide, a target for antiretroviral therapy .2004 Add to clipboard 14: Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology.2003 Add to clipboard 15: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia.2002 Add to clipboard 16: Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy .2002 Add to clipboard 17: Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy .2002 Add to clipboard 18: Human immunodeficiency virus type 1 quasi species that rebound after discontinuation of highly active antiretroviral therapy are similar to the viral quasi species present before initiation of therapy.2001 Add to clipboard 19: CD95 (APO-1/Fas) expression on naive CD4(+) T cells increases with disease progression in HIV-infected children and adolescents: effect of highly active antiretroviral therapy (HAART).2001 Add to clipboard 20: Effect of highly active antiretroviral therapy on the natural history of anal squamous intraepithelial lesions and anal human papillomavirus infection.2001 Add to clipboard 21: Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy .2000 Add to clipboard 22: Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients.2000 Add to clipboard 23: T cell responses to recall antigens, alloantigen, and mitogen of HIV-infected patients receiving long-term combined antiretroviral therapy .2000 Add to clipboard 24: Reconstitution of human thymic implants is limited by human immunodeficiency virus breakthrough during antiretroviral therapy .1999 Add to clipboard 25: Natural history of HIV infection in the era of combination antiretroviral therapy .1999 Add to clipboard 26: Inhibition of human immunodeficiency virus type 1 long terminal repeat-driven transcription by an in vivo metabolite of oltipraz: implications for antiretroviral therapy .1996 Add to clipboard 27: NIH conference. Antiretroviral therapy in AIDS.1990 Add to clipboard 28: Murine models for evaluating antiretroviral therapy .1990 Add to clipboard 最新研究报道 PNAS：T细胞阻断艾滋病病毒机理被揭示或许能为艾滋病的预防和治疗提供新思路美国杜克大学和美国西奈山医学院的科学家揭示了一种宿主蛋白在抑制艾滋病病毒复制过程中发挥其重要作用的机理。研究人员称，该发现或许能为艾滋病的预防和治疗提供新的思路。相关论文发表在最新一期的美国《国家科学院院刊》（ PNAS ）上。据介绍，CD8+T细胞是人体中一种重要的免疫细胞，在艾滋病感染初期，该细胞具有抑制艾滋病病毒复制和传播的作用。该研究小组此前的研究已发现，人体中一种名为前胸腺素-的宿主蛋白在其中发挥着重要的作用，但并不清楚其中具体原理。新的研究发现，前胸腺素-能刺激机体产生出干扰素，在干扰素的作用下，CD8+T细胞的抗病毒活性得以维持。研究人员利用小鼠和人类细胞进行了一系列实验，结果表明，前胸腺素-能够与一种被称为TLR4的重要细胞受体结合在一起，并刺激其产生干扰素。干扰素是人体先天免疫系统的一部分，它能通过细胞表面受体作用使细胞产生抗病毒蛋白，从而杀死包括丙肝病毒和艾滋病病毒在内的多种病原体，同时还可增强自然杀伤细胞、巨噬细胞和T淋巴细胞的活力，起到免疫调节的作用。负责该研究的美国杜克大学医学院主任玛丽科洛特曼说：我们发现这是一个十分有趣的过程，通常情况下，只有采用引入病毒侵入的方式才能诱发产生干扰素。而这次我们却发现，引发这一反应的是我们身体系统中的一种宿主蛋白，这是人体免疫系统协同工作的一个完美案例。此外，研究人员还将巨噬细胞作为一个主要的研究对象，这种免疫细胞是人体抵御病毒和微生物的第一道防线，同时也是艾滋病病毒入侵的主要对象。科洛特曼说，巨噬细胞也很重要，因为研究发现，艾滋病病毒在入侵过程中，会在巨噬细胞内聚集和繁殖，从而使人体免疫系统受损，甚至完全遭到破坏。研究人员称，下一步他们将对前胸腺素-的特殊结构等特征展开研究，以揭开其刺激机体产生干扰素的过程，这将会为包括艾滋病在内的多种疾病的预防和治疗提供新的思路。更多阅读美国每日科学网站相关报道（英文）《国家科学院院刊》发表论文摘要（英文）南开教师抑制艾滋病病毒大胆构想获盖茨十万美金资助《自然》：科学家揭开人体抵抗艾滋病病毒之谜法国合成阻断艾滋病病毒传播的分子

个人分类: 知识发现|2041 次阅读|0 个评论

艾滋病病毒整合酶研究的信息分析与相关基因知识发现

xupeiyang 2010-2-2 13:34

http://www.gopubmed.org/web/gopubmed/1?WEB067kk1vt0pwuqIsI1I00f01000j10040001rl Integrase and HIV and viral DNA 737 documents semantically analyzed 1 2 Top Years Publications 2009 73 2008 62 2006 50 2007 49 2001 47 2002 44 2005 41 1995 41 2004 39 2000 39 1999 36 1994 35 2003 34 1997 28 1996 27 1993 24 1998 22 1992 14 1991 9 2010 6 1 2 1 2 Top Countries Publications USA 395 France 92 Japan 28 Belgium 28 Italy 17 Netherlands 17 Germany 16 Australia 14 Canada 14 United Kingdom 14 China 11 Israel 10 South Korea 9 Switzerland 9 Russia 9 Spain 5 India 5 Czech Republic 4 Austria 4 South Africa 3 1 2 1 2 3 ... 8 Top Cities Publications Bethesda 60 Boston 28 Philadelphia 27 Leuven 22 New York 21 Los Angeles 21 Paris 19 Frederick 18 Bordeaux 16 Amsterdam 16 Cachan 14 Villejuif 14 Tokyo 14 St. Louis 13 Stanford 13 Montreal 9 Rome 9 London 8 San Francisco 8 Baltimore 8 1 2 3 ... 8 1 2 3 ... 10 Top Journals Publications J Virol 149 J Biol Chem 46 Nucleic Acids Res 28 P Natl Acad Sci Usa 27 Virology 24 J Mol Biol 21 Retrovirology 20 Biochemistry-us 17 J Med Chem 15 Aids Res Hum Retrov 15 Embo J 10 Science 9 Biochem Bioph Res Co 9 Plos Pathog 8 Antimicrob Agents Ch 8 Mol Pharmacol 8 Mol Ther 7 Bioorg Med Chem Lett 7 J Virol Methods 6 J Gen Virol 6 1 2 3 ... 10 1 2 3 ... 138 Top Terms Publications Integrases 693 Viruses 668 integrase activity 664 integrase 640 HIV-1 636 DNA 582 HIV 508 DNA, Viral 465 Humans 451 Proteins 385 HIV Integrase 361 Virus Integration 266 Base Sequence 238 Genome 237 Genomics 236 Enzymes 219 Virus Replication 219 Zidovudine 217 Mutation 195 viral genome replication 177 1 2 3 ... 138 1 2 3 ... 126 Top Authors Publications Bushman F 35 Pommier Y 35 Mouscadet J 28 Neamati N 26 Engelman A 25 Skalka A 22 Debyser Z 19 Litvak S 18 Craigie R 18 Chow S 17 Plasterk R 16 Parissi V 15 Mazumder A 15 Auclair C 13 Marchand C 12 Leh H 12 Burke T 12 Gottikh M 12 De Soultrait V 12 Katzman M 12 1 2 3 ... 126 http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi Start A-Literature C-Literature B-list Filter Literature A-query: Integrase and HIV C-query: HIV and viral DNA The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 737 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 32176 and can be accessed from the start page after you leave this session. There are 250 terms on the current B-list ( 116 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. Rank Prob B-term 10.99gp120 20.99gp41 30.99immunodeficiency virus genome 40.99vif 50.99virus genome 60.99cd34 70.99nef 80.99nuclear localization signal 90.99ccr5 100.99vpr 110.99hiv-1 ltr 120.99g quartet 130.99catalytic domain 140.99hiv-1 gene 150.99polyprotein 160.99terminal repeat 170.99chemokine 180.99gag pol 190.99gene human immunodeficiency 200.99importin 210.99topoisomerase 220.99cd8 230.99cyclophilin 240.99transcription factor 250.99rag2 260.99hiv-1 pol gene 270.99retrotransposon 280.99catalytic core 290.99nucleocapsid protein 300.99chemokine receptor 310.99rnase 320.99viral genome 330.99cdna 340.99pol gene 350.99protease gene human 360.99protease gene 370.99topoisomerase i 380.99murine leukemia virus 390.98capsid 400.98cd38 410.98cd4 420.98gene transfer lentiviral 430.98ltr 440.98rna genome 450.98dna binding 460.98hsv-1 470.98tat 480.98transgene expression 490.98virus polymerase gene 500.97nucleoporin 510.97vector gene 520.97gene hiv 530.97rt 540.97transgene 550.97pcr 560.96gene transfer 570.96rna polymerase 580.96v1 590.95gag 600.95hiv 610.95u3 620.95sustained transgene expression 630.95human genome 640.95virus rna genome 650.95siv 660.95p51 670.94endonuclease 680.94gene human 690.94ini1 700.94dna sequence 710.94pol 720.94reporter gene 730.93virus pol gene 740.93p66 750.92enhancer 760.92prion protein 770.91genomic 780.89clone 790.88ubiquitin 800.87polymerase 810.86genome 820.85idsa 830.84lys 840.83rna 850.82region pol gene 860.82pol gene hiv 870.81domain 880.81promoter 890.81p6 900.81ccr2 910.80mg2 920.79proteinase 930.79dna sequence specific 940.76protease 950.75sar 960.75immune response 970.74ribonuclease 980.73lc 990.73fret 1000.72hla 1010.70template 1020.65exonuclease 1030.64m d 1040.64fda 1050.60coiled coil 1060.60fusion 1070.60p21 1080.57switch 1090.56class i 1100.55glycoprotein 1110.53decay 1120.52myc 1130.51cys 1140.50nmr 1150.50tran 1160.471h 1170.46gene 1180.45rag 1190.43lens 1200.42box 1210.42tumor necrosis factor 1220.40region viral genome 1230.39core 1240.38nuclear protein 1250.38pis 1260.37spot 1270.35signal 1280.34cycle 1290.31line 1300.30b f 1310.28ex 1320.26novel 1330.25aid 1340.25acer 1350.25region 1360.24proteolysis 1370.24sera 1380.22nuclease 1390.20protein kinase 1400.19co 1410.18step 1420.17bcg 1430.17e coli 1440.17lack 1450.16impact 1460.16protein 1470.16transporter 1480.15asp 1490.15inhibitor 1500.14variant 1510.14protein gene 1520.13hope 1530.13ligand 1540.13fragment 1550.12cpz 1560.12cape 1570.11block 1580.11term 1590.11group 1600.10factor gene 1610.10non 1620.10p1 1630.10p2 1640.09alga 1650.09early 1660.09milk 1670.08igg 1680.08sp 1690.08ion 1700.08cell 1710.06not 1720.06cd 1730.05activity 1740.05bis 1750.05synergistic 1760.05gs 1770.05ag 1780.04fused 1790.04live 1800.04mode 1810.04leaf 1820.03past 1830.03cis 1840.03a1 1850.03mass 1860.03cholesterol 1870.03phosphate 1880.03kinase 1890.03base 1900.02inactive 1910.02king 1920.02total 1930.02hat 1940.02mn 1950.02card 1960.02start 1970.02double 1980.02amp 1990.02map 2000.01family 2010.01ring 2020.01point 2030.01salt 2040.01end 2050.01mice 2060.01year 2070.01ca 2080.01key 2090.01mark 2100.01nervous 2110.01b 2120.01old 2130.01art 2140.01minor 2150.01low 2160.01ray 2170.01tert 2180.01lethal 2190.01gas 2200.01modification 2210.01phase 2220.01alpha 2230.00side 2240.00time 2250.00care 2260.00receptor 2270.00going 2280.00large 2290.00beta 2300.00act 2310.00simple 2320.00pre 2330.00segment 2340.00fast 2350.00far 2360.00g 2370.00ab 2380.00set 2390.00gamma 2400.00or 2410.00vs 2420.00membrane 2430.00ma 2440.00reductase 2450.00fit 2460.00secretion 2470.00path 2480.00safe 2490.00nine 2500.00a Restrict by semantic categories? job id # 32176 started Tue Feb 2 03:07:26 2010 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 32176 Search ARROWSMITH A A_query_raw: Integrase and HIV Tue Feb 2 03:07:42 2010 A query = Integrase and HIV started Tue Feb 2 03:07:43 2010 A query resulted in 1906 titles 32176 Search ARROWSMITH C C_query_raw: HIV and viral DNA Tue Feb 2 03:08:02 2010 C: HIV and viral DNA 13339 A: pubmed_query_A 1906 AC: ( Integrase and HIV ) AND ( HIV and viral DNA ) 737 C query = HIV and viral DNA started Tue Feb 2 03:08:06 2010 C query resulted in 13339 titles A AND C query resulted in 737 titles 3779 B-terms ready on Tue Feb 2 03:09:37 2010 Sem_filter: Genes Molecular Sequences, and Gene Protein Names 250 B-terms left after filter executed Tue Feb 2 03:12:01 2010 B-list on Tue Feb 2 03:12:51 2010 1 gp120 2 gp41 3 immunodeficiency virus genome 4 vif 5 virus genome 6 cd34 7 nef 8 nuclear localization signal 9 ccr5 10 vpr 11 hiv-1 ltr 12 g quartet 13 catalytic domain 14 hiv-1 gene 15 polyprotein 16 terminal repeat 17 chemokine 18 gag pol 19 gene human immunodeficiency 20 importin 21 topoisomerase 22 cd8 23 cyclophilin 24 transcription factor 25 rag2 26 hiv-1 pol gene 27 retrotransposon 28 catalytic core 29 nucleocapsid protein 30 chemokine receptor 31 rnase 32 viral genome 33 cdna 34 pol gene 35 protease gene human 36 protease gene 37 topoisomerase i 38 murine leukemia virus 39 capsid 40 cd38 41 cd4 42 gene transfer lentiviral 43 ltr 44 rna genome 45 dna binding 46 hsv-1 47 tat 48 transgene expression 49 virus polymerase gene 50 nucleoporin 51 vector gene 52 gene hiv 53 rt 54 transgene 55 pcr 56 gene transfer 57 rna polymerase 58 v1 59 gag 60 hiv 61 u3 62 sustained transgene expression 63 human genome 64 virus rna genome 65 siv 66 p51 67 endonuclease 68 gene human 69 ini1 70 dna sequence 71 pol 72 reporter gene 73 virus pol gene 74 p66 75 enhancer 76 prion protein 77 genomic 78 clone 79 ubiquitin 80 polymerase 81 genome 82 idsa 83 lys 84 rna 85 region pol gene 86 pol gene hiv 87 domain 88 promoter 89 p6 90 ccr2 91 mg2 92 proteinase 93 dna sequence specific 94 protease 95 sar 96 immune response 97 ribonuclease 98 lc 99 fret 100 hla 101 template 102 exonuclease 103 m d 104 fda 105 coiled coil 106 fusion 107 p21 108 switch 109 class i 110 glycoprotein 111 decay 112 myc 113 cys 114 nmr 115 tran 116 1h Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature Integrase and HIV gp120 HIV and viral DNA 1: Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4.2005 Add to clipboard 2: Human immunodeficiency virus glycoprotein gp120 as the primary target for the antiviral action of AR177 (Zintevir).1998 Add to clipboard 1: Evolution of proviral gp120 over the first year of HIV-1 subtype C infection.2009 Add to clipboard 2: Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.2009 Add to clipboard 3: A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors.2009 Add to clipboard 4: Structure-function analysis of human immunodeficiency virus type 1 gp120 amino acid mutations associated with resistance to the CCR5 coreceptor antagonist vicriviroc.2009 Add to clipboard 5: 2009 Add to clipboard 6: Removal of a single N-linked glycan in human immunodeficiency virus type 1 gp120 results in an enhanced ability to induce neutralizing antibody responses.2008 Add to clipboard 7: Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1 gp120 envelope.2008 Add to clipboard 8: Mapping resistance to the CCR5 co-receptor antagonist vicriviroc using heterologous chimeric HIV-1 envelope genes reveals key determinants in the C2-V5 domain of gp120 .2008 Add to clipboard 9: Improved induction of antibodies against key neutralizing epitopes by human immunodeficiency virus type 1 gp120 DNA prime-protein boost vaccination compared to gp120 protein-only vaccination.2008 Add to clipboard

个人分类: 信息分析|1877 次阅读|0 个评论

艾滋病病毒逃脱免疫监控研究进展

xupeiyang 2009-9-24 15:59

http://www.bioon.com/biology/sars/409730.shtml 来源生命经纬 2009-9-23 9:32:57 PLoSPathogens： HIV可利用多种途径逃脱免疫监控据一篇发表于 Public Library of Science Pathogens 杂志的研究报告，埃默里疫苗中心的研究人员发现，艾滋病病毒可以通过多种途径避开机体中的免疫系统。在一般病毒感染初期，人类免疫系统能够产生相应的中和抗体，中和抗体能与病毒表面抗原结合，从而阻止该病原微生物粘附靶细胞受体，防止侵入细胞。但问题在于，HIV具有极强的突变能力，这使得中和抗体无法识别各种类型的HIV突变体。该课题组的研究表明，即使研究人员能找到疫苗中的某个特定的部分，该部分能够刺激产生中和抗体，HIV快速突变的能力仍然可能由多种因素引起。据介绍，机体内单一类型的中和细胞并不足以遏制HIV。研究人员Derdeyn及其同事在赞比亚进行该研究，研究对象是有一个确诊为HIV阳性的夫妻。他们抽取了初期HIV感染者的血液样品，并对感染HIV两年的患者的血液进行病毒分离，以观察患者自身的抗体是如何中和这些病毒的。研究发现，在这两类患者中，一些病毒的外蛋白发生突变，在突变后，某种酶更易连接到糖分子上，从而干扰了抗体攻击病毒。而且，在这两类患者中，其HIV的遗传密码也有多处发生改变，这也是HIV容易逃脱中和抗体攻击的原因。该研究结果意味着要对HIV感染免疫，人体需要多种类型的中和抗体共同发挥作用。（生物谷 Bioon.com）生物谷推荐原始出处： PLoS Pathog 5(9): e1000594. doi:10.1371/journal.ppat.1000594 Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways Rong Rong1,2, Bing Li2, Rebecca M. Lynch1,2, Richard E. Haaland1,2, Megan K. Murphy1,2, Joseph Mulenga3,4, Susan A. Allen3,5, Abraham Pinter6,7, George M. Shaw8, Eric Hunter1,2, James E. Robinson9, S. Gnanakaran10, Cynthia A. Derdeyn1,2* 1 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America, 2 Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America, 3 Zambia Emory HIV Research Project, ZEHRP, Lusaka, Zambia, 4 Zambia Blood Transfusion Service, Lusaka, Zambia, 5 Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America, 6 Public Health Research Institute, Newark, New Jersey, United States of America, 7 New Jersey School of Medicine, University of Medicine and Dentistry, Newark, New Jersey, United States of America, 8 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 9 Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, United States of America, 10 Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection. Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection. To provide a detailed portrayal of the escape pathways, Nab resistant variants identified at multiple time points were used to create a series of envelope (Env) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection, and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization. http://www.gopubmed.org/web/gopubmed/1?WEB01p4tdnztaexe7I3sI2I00d000j10040001rl Top Years Publications 2009 3 2008 3 2006 2 2004 2 2007 1 2001 1 1997 1 1996 1 Top Countries Publications USA 9 Italy 2 France 1 Netherlands 1 Canada 1 Top Cities Publications Rome 2 Atlanta 1 Paris 1 Birmingham, USA 1 San Diego 1 Amsterdam 1 Seattle 1 Philadelphia 1 Bethesda 1 San Francisco 1 Hamilton, Canada 1 Top Journals Publications J Virol 3 Plos Pathog 1 Apoptosis 1 Infection 1 Curr Opin Hiv Aids 1 Plos Comput Biol 1 Faseb J 1 J Exp Med 1 Aids 1 J Leukocyte Biol 1 Nat Med 1 Microbiol Rev 1 1 2 3 ... 18 Top Terms Publications HIV-1 14 Viruses 13 HIV 12 Humans 10 Mutation 8 Immunization 7 Immunity 7 Vaccines 5 Vaccination 5 T-Lymphocytes 5 HIV Infections 5 Acquired Immunodeficiency Syndrome 5 Genes 5 Virus Replication 5 Pressure 4 Patients 4 Antibodies 4 antigen binding 4 host cell 4 pathogenesis 4 1 2 3 ... 18 1 2 3 4 5 Top Authors Publications Hahn B 2 Piacentini M 1 Gougeon M 1 Santoro M 1 Bertoli A 1 Lorenzini P 1 Ceccherini-Silberstein F 1 Gianotti N 1 Mussini C 1 Torti C 1 Di Perri G 1 Barbarini G 1 Bini T 1 Melzi S 1 Caramello P 1 Maserati R 1 Narciso P 1 Micheli V 1 Antinori A 1 Perno C 1 1 2 3 4 5 相关研究报道： Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways . PMID: 19763269 Related Articles Authors: Rong, R , Li, B , Lynch, R M , Haaland, R E , Murphy, M K , Mulenga, J , Allen, S A , Pinter, A , Shaw, G M , Hunter, E , Robinson, J E , Gnanakaran, S , Derdeyn, C A Journal: PLoS Pathog , Vol. 5 (9): e1000594 , 2009 Abstract: One aim for an HIV vaccine is to elicit neutralizing antibodies (Nab) that can limit replication of genetically diverse viruses and prevent establishment of a new infection . Thus, identifying the strengths and weaknesses of Nab during the early stages of natural infection could prove useful in achieving this goal. Here we demonstrate that viral escape readily occurred despite the development of high titer autologous Nab in two subjects with acute/early subtype C infection . To provide a detailed portrayal of the escape pathways , Nab resistant variants identified at multiple time points were used to create a series of envelope ( Env ) glycoprotein chimeras and mutants within the background of a corresponding newly transmitted Env. In one subject, Nab escape was driven predominantly by changes in the region of gp120 that extends from the beginning of the V3 domain to the end of the V5 domain (V3V5). However, Nab escape pathways in this subject oscillated and at times required cooperation between V1V2 and the gp41 ectodomain. In the second subject, escape was driven by changes in V1V2. This V1V2-dependent escape pathway was retained over time, and its utility was reflected in the virus's ability to escape from two distinct monoclonal antibodies (Mabs) derived from this same patient via introduction of a single potential N-linked glycosylation site in V2. Spatial representation of the sequence changes in gp120 suggested that selective pressure acted upon the same regions of Env in these two subjects, even though the Env domains that drove escape were different. Together the findings argue that a single mutational pathway is not sufficient to confer escape in early subtype C HIV-1 infection , and support a model in which multiple strategies, including potential glycan shifts, direct alteration of an epitope sequence, and cooperative Env domain conformational masking, are used to evade neutralization. Affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta , Georgia, United States of America. Wikipedia: AIDS Virus , Active immunization , Animal virus , Antibodies , Antibodies, monoclonal , Antigenic determinants , Client , Epitopes , Genetic diversity , Genetic variation , Glycans , Glycoprotein , Glycosylation , HIV , HIV-1 , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Monoclonal antibodies , Mutation , Nature , Patient , Polysaccharides , Pressure , Vaccination , Vaccines , Variation (genetics) , Virus Title: New insights on the role of apoptosis and autophagy in HIV pathogenesis. PMID: 19199038 Related Articles Authors: Gougeon, M L , Piacentini, M Journal: Apoptosis , Vol. 14 (4): 501-8 , 2009 Abstract: Viruses manipulate host cells to ensure their own survival and, at late stages of the viral life cycle, they kill the infected target cell to ensure their propagation. In addition, some viruses induce a bystander killing, a viral strategy to escape from the host's innate and cognate defense systems. In HIV- infection , the disabling of the immune system is initially due to the preferential depletion by apoptosis of virus-specific CD4(+) T cells in lymphoid tissues, followed by the destruction of non-infected bystander cells. Both the extrinsic and the intrinsic pathways are activated, and this is the consequence of systemic immune activation. This review presents recent developments showing that the gastrointestinal tract is the major reservoir of infected cells and the site of rapid and profound loss of CD4 T cells, and that microbial translocation from the gastrointestinal tract is the cause of immune activation. Furthermore, apoptosis mechanisms involved in HIV-induced neuropathological disorders are discussed, including the role of syncytia that involve the sequential activation of ATM , p38MAPK and p53 . Finally, HIV-associated dementia (HAD) was recently found in monkey models to be linked to inhibition of autophagy in neurons, suggesting that homeostasis of autophagy is a reliable security factor for neurons, and challenging the development of new therapeutics aimed at boosting neuronal autophagy to prevent HAD. Affiliation: Antiviral Immunity, Biotherapy and Vaccine Unit, Institut Pasteur, Paris , France . mlgougeo@pasteur.fr Pubmed MeSH: AIDS Dementia Complex , Acquired Immunodeficiency Syndrome , Animals , CD4-Positive T-Lymphocytes , Cell Cycle Proteins , DNA-Binding Proteins , Enzyme Activation , HIV Infections , HIV-1 , Humans , Protein-Serine-Threonine Kinases , Tumor Suppressor Protein p53 , Tumor Suppressor Proteins , p38 Mitogen-Activated Protein Kinases Wikipedia: AIDS Virus , Active immunity , Animal virus , Anthropoidea , Anthropoids , Apoptosis , Autophagocytosis , Autophagy , Autoregulation , Dementia , Digestive tract , Frontotemporal lobar degeneration , GI tract , Gastrointestinal Tract , Giant cell , HIV , HTLV-III , Haplorhini , Homeostasis , Human Immunodeficiency Virus , Immune System , Immune systems , Immunity , Immunization , Life cycle , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Lymphatic tissue , Lymphoid Tissue , Monkey , Multinucleated giant cells , Nerve cell , Neuron , Semantic Dementia , Syncytia , Syncytium , T-Cell , T-lymphocyte , T Lymphocytes , T cells , Therapeutic , Tissue , Treatment , Variolation , Virus Title: Two different patterns of mutations are involved in the genotypic resistance score for atazanavir boosted versus unboosted by ritonavir in multiple failing patients. PMID: 19169632 Related Articles Authors: Santoro, M M , Bertoli, A , Lorenzini, P , Ceccherini-Silberstein, F , Gianotti, N , Mussini, C , Torti, C , Di Perri, G , Barbarini, G , Bini, T , Melzi, S , Caramello, P , Maserati, R , Narciso, P , Micheli, V , Antinori, A , Perno, C F , care study group Journal: Infection , Vol. 37 (3): 233-43 , 2009 Abstract: OBJECTIVES: The protease inhibitor atazanavir (ATV) can be used either boosted by ritonavir (ATV300/r) or unboosted (ATV400). To date, however, genotypic resistance scores (GRSs) have been developed only for boosted-ATV. We have determined GRS associated with virologic response (VR) for both ATV300/r and ATV400 in highly pre-treated HIV-1 infected patients. PATIENTS AND METHODS: We analyzed the results of genotypic tests available 0-3 months before the initiation of an ATV-containing regimen in 159 patients with HIV-RNA or= 500 copies/ml (ATV300/r group: 74; ATV400 group: 85) who were enrolled in the CARe study through an Early Access Program. The impact of baseline protease mutations on VR (or= 1 log(10)copies/ml HIV-RNA decrease at 12-24 weeks) was analyzed using Fisher's exact test. Mutated protease amino acid positions (MPP) with p 0.20 were retained for further analysis. The GRSs were determined by a step-by-step analysis using the chi(2) test for trend. RESULTS: The GRSs for ATV300/r and ATV400 revealed differing sets of mutations. For ATV300/r, 12 MPPs (10C/I/V + 32I + 34Q + 46I/L + 53L + 54A/M/V + 82A/F/I/T + 84V + 90M - 15E /G/L/V - 69K/M/N/Q/R/T/Y - 72M/ T/V; p = 1.38 x 10(-9)) were the most strongly associated with VR (VR: 100%, 78.3%, 83.3%, 75% and 0% of patients with a score of -2/-1, 0, 1, 2, and or= 3, respectively); the last three MPPs (I15/H69/I72) were associated with a better VR. For ATV400, nine MPPs (16E + 20I/M/R/T/V + 32I + 33F/I/V + 53L/Y + 64L/M/ V + 71I/T/V + 85V + 93L/M; p = 9.42 x 10(-8)) were most strongly associated with VR (VR: 83.3%, 66.7%, 5.9%, 0% of patients with 0, 1/2, 3, and or= 4 MPP, respectively). Differences between GRSs for ATV300/r and ATV400 may be due to different ATV drug levels (boosted vs unboosted), favoring different pathways of escape from antiviral pressure. CONCLUSIONS: Both GRSs were independent predictors of response in a multivariable logistic regression model. Nevertheless, cross-validation of these GRSs on different patient databases is required before their implementation in clinical practice. Affiliation: Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome , Italy . Pubmed MeSH: Amino Acid Sequence , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , Chi-Square Distribution , Codon , Drug Resistance, Multiple, Viral , Drug Resistance, Viral , Drug Synergism , HIV Infections , HIV Protease Inhibitors , Humans , Longitudinal Studies , Multivariate Analysis , Oligopeptides , Prospective Studies , Pyridines , RNA, Viral , Treatment Outcome , Viral Load , Viremia Wikipedia: Administration , Amino Acids , Antiviral agents , Antiviral drugs , Antivirals , Client , Drugs , Genotype , HIV-1 , Human immunodeficiency virus 1 , Logistic model , Logistic regression , Logistics , Logit model , Mutation , Norvir , Patient , Peptide hydrolases , Pressure , Protease inhibitor , Proteases , Ritonavir , Supervision Title: Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing. PMID: 18256145 Related Articles Authors: Salazar-Gonzalez, J F , Bailes, E , Pham, K T , Salazar, M G , Guffey, M B , Keele, B F , Derdeyn, C A , Farmer, P , Hunter, E , Allen, S , Manigart, O , Mulenga, J , Anderson, J A , Swanstrom, R , Haynes, B F , Athreya, G S , Korber, B T , Sharp, P M , Shaw, G M , Hahn, B H Journal: J Virol , Vol. 82 (8): 3952-70 , 2008 Abstract: Accurate identification of the transmitted virus and sequences evolving from it could be instrumental in elucidating the transmission of human immunodeficiency virus type 1 ( HIV-1 ) and in developing vaccines, drugs, or microbicides to prevent infection . Here we describe an experimental approach to analyze HIV-1 env genes as intact genetic units amplified from plasma virion RNA by single-genome amplification (SGA), followed by direct sequencing of uncloned DNA amplicons. We show that this strategy precludes in vitro artifacts caused by Taq-induced nucleotide substitutions and template switching, provides an accurate representation of the env quasispecies in vivo, and has an overall error rate (including nucleotide misincorporation, insertion, and deletion) of less than 8 x 10(-5). Applying this method to the analysis of virus in plasma from 12 Zambian subjects from whom samples were obtained within 3 months of seroconversion, we show that transmitted or early founder viruses can be identified and that molecular pathways and rates of early env diversification can be defined. Specifically, we show that 8 of the 12 subjects were each infected by a single virus, while 4 others acquired more than one virus; that the rate of virus evolution in one subject during an 80-day period spanning seroconversion was 1.7 x 10(-5) substitutions per site per day; and that evidence of strong immunologic selection can be seen in Env and overlapping Rev sequences based on nonrandom accumulation of nonsynonymous mutations. We also compared the results of the SGA approach with those of more-conventional bulk PCR amplification methods performed on the same patient samples and found that the latter is associated with excessive rates of Taq-induced recombination, nucleotide misincorporation, template resampling, and cloning bias. These findings indicate that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately. Affiliation: Department of Medicine, University of Alabama at Birmingham, 720 20th Street South, Kaul 816, Birmingham , AL 35294, USA . Pubmed MeSH: Amino Acid Substitution , Evolution, Molecular , Humans , Nucleic Acid Amplification Techniques , Phylogeny , Plasma , RNA, Viral , Selection (Genetics) , Sequence Analysis, DNA , Sequence Homology , env Gene Products, Human Immunodeficiency Virus , rev Gene Products, Human Immunodeficiency Virus Wikipedia: AIDS Virus , Active immunization , Amplifier , Animal virus , Antimicrobial agents , Artefact , Artifact , B-DNA , Bias , Cistron , Client , DNA , Deoxyribonucleic Acid , Drugs , Ecological fallacy , Evolution , Gene , Genetic material , Genetic recombination , Genome , Genomics , HIV , HIV-1 , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Immunity , Immunization , Inverse PCR , Inverse polymerase chain reaction , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Mutation , Nested PCR , Nested polymerase chain reaction , Nucleotides , PCR , Patient , Polymerase Chain Reaction , RNA , Recombination , Recombination, genetic , RiboNucleic Acid , Statistical bias , Systematic bias , Vaccination , Vaccines , Variolation , Virion , Virus Title: Antibody responses in primary HIV-1 infection . PMID: 19372943 Related Articles Authors: Frost, S D , Trkola, A , Gnthard, H F , Richman, D D Journal: Curr Opin HIV AIDS , Vol. 3 (1): 45-51 , 2008 Abstract: PURPOSE OF REVIEW: HIV-1 establishes persistent infections characterized by high levels of viral replication. This finding is remarkable given the presence of apparently vigorous HIV-specific cellular and humoral immune responses. We review the dynamics of antibody responses and viral escape from these responses during primary HIV-1 infection . RECENT FINDINGS: Many B cell dysfunctions appear early in HIV-1 infection , and compromise humoral responses to HIV-1 and other pathogens. The rate of viral escape from autologous neutralization varies greatly between individuals with primary HIV-1 infection , and is on average higher than the rate of escape in chronically infected individuals. Mutations, changes in glycosylation and insertions and deletions in the viral envelope may all contribute to viral escape . There may be differences in neutralization sensitivity and evolution of neutralization escape between different HIV-1 subtypes. Although several broadly neutralizing monoclonal antibodies have been identified, the factors that contribute to the development of broad heterologous responses remain unclear. SUMMARY: The rapid escape of HIV-1 in response to neutralizing antibodies and the plethora of B cell dysfunctions that occur during HIV infection pose significant obstacles to the design of an effective HIV-1 vaccine. The study of large cohorts of individuals enrolled during primary HIV-1 infection using high-throughput immunoassays, sequencing of the virus and the host, and new statistical tools may help to elucidate the pathways of viral escape , to elicit broadly neutralizing antibody responses, and to suggest means of minimizing the impact of HIV-1 on humoral immunity. Affiliation: aDepartment of Pathology, University of California, San Diego, California, USA bDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland cSchool of Medicine, University of California, USA dVeterans Affairs San Diego Healthcare System, San Diego , California , USA . Wikipedia: AIDS Virus , Active immunization , Animal virus , Antibodies , Antibodies, monoclonal , Antibody , B-Cell , B-lymphocyte , B Cells , B cell receptor , B lymphocytes , Cell-mediated immunity , Evolution , Glycosylation , HIV , HIV-1 , HIV infection , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Humoral immune response , Humoral immunity , Immune response , Immunity , Immunization , Immunoassay , Immunoglobulin , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Monoclonal antibodies , Mutation , Opsonin , Pathogenicity , T-cell mediated immunity , Vaccination , Vaccines , Variolation , Viral envelope , Viral membrane , Viral replication , Virulence , Virus Title: RNA structure modulates splicing efficiency at the human immunodeficiency virus type 1 major splice donor. PMID: 18160437 Related Articles Authors: Abbink, T E , Berkhout, B Journal: J Virol , Vol. 82 (6): 3090-8 , 2008 Abstract: The untranslated leader of the human immunodeficiency virus type 1 ( HIV-1 ) RNA genome encodes essential sequence and structural motifs that control various replication steps. The 5' splice site or splice donor (SD) is embedded in a semistable hairpin, but the function of this structure is unknown. We stabilized this SD hairpin by creating an additional base pair and demonstrated a severe HIV-1 replication defect. A splicing defect was apparent in RNA analyses of virus-infected cells and cells transfected with appropriate reporter constructs. We selected multiple virus revertants in search for interesting second-site escape pathways . Most revertants acquired an additional mutation that modulated the stability of the mutant SD hairpin. One revertant acquired a single nucleotide change in the upstream DIS hairpin. We demonstrate that a novel SD site is created by this upstream mutation, which obviously reduces the number of leader nucleotides that are included in spliced HIV-1 transcripts. These results suggest a novel role of RNA structure in the regulation of HIV-1 splicing. Affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam , The Netherlands . Pubmed MeSH: Base Sequence , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Genes, Reporter , Humans , Nucleic Acid Conformation , RNA Splicing , RNA, Viral , Virus Replication Wikipedia: AIDS Virus , Animal virus , Base pair , Base pairing , Donor , Genome , Genomics , HIV , HIV-1 , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Mutation , Nucleotides , Organ donor , RNA , RiboNucleic Acid , Virus Coping with viral diversity in HIV vaccine design. PMID: 17465674 Related Articles Authors: Nickle, D C , Rolland, M , Jensen, M A , Pond, S L , Deng, W , Seligman, M , Heckerman, D , Mullins, J I , Jojic, N Journal: PLoS Comput Biol , Vol. 3 (4): e75 , 2007 Abstract: The ability of human immunodeficiency virus type 1 ( HIV-1 ) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection . The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree ) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT (+) antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus. Affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle , Washington , United States of America. Pubmed MeSH: Antigenic Variation , Drug Design , Epitope Mapping , nef Gene Products, Human Immunodeficiency Virus Wikipedia: AIDS Virus , Active immunization , Animal virus , Antigen , Antigen presentation , Antigen processing , Cistron , Gene , Gene products, gag , Genetic diversity , Genetic material , Genetic variation , HIV , HIV-1 , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Immunity , Immunization , Indigenous population , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Mutation , Native-born , Native born , Natives , Nef gene product , Pressure , Proteins , Tribes , Vaccination , Vaccines , Variation (genetics) , Variolation , Virus Title: The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS. PMID: 17077296 Related Articles Authors: Quaranta, M G , Mattioli, B , Giordani, L , Viora, M Journal: FASEB J , Vol. 20 (13): 2198-208 , 2006 Abstract: Dendritic cells (DC) play a crucial role in the generation and regulation of immunity, and their interaction with HIV is relevant in the pathogenesis of AIDS favoring both the initial establishment and spread of the infection and the development of antiviral immunity. HIV-1 Nef is an essential factor for efficient viral replication and pathogenesis, and several studies have been addressed to assess the possible influence of endogenous or exogenous Nef on DC biology. Our findings and other reported data described in this review demonstrate that Nef subverts DC biology interfering with phenotypical, morphological, and functional DC developmental programs, thus representing a viral tool underlying AIDS pathogenesis. This review provides an overview on the mechanism by which Nef , hijacking DC functional activity, may favor both the replication of HIV-1 and the escape from immune surveillance. Overall, the findings described here may contribute to the understanding of Nef function, mechanism of action, and cellular partners. Further elucidation of genes induced through Nef signaling in DC could reveal pathways used by DC to drive HIV spread and will be critical to identify therapeutic strategies to bias the DC system toward activation of antiviral immunity instead of facilitating virus dissemination. Affiliation: Department of Drug Research and Evaluation, Istituto Superiore di Sanit, Viale Regina Elena 299, 00161 Rome , Italy . Pubmed MeSH: CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Gene Products, nef , Humans , Killer Cells, Natural , nef Gene Products, Human Immunodeficiency Virus Wikipedia: AIDS , AIDS Virus , Acquired Immune Deficiency Syndrome , Acquired Immunodeficiency Syndrome , Animal virus , Antiviral agents , Antiviral drugs , Antivirals , Biology , Cistron , Cytotoxin , Dendrite , Dendritic Cell , Dendritic cells , Endotoxin , Enterotoxin , Exogen , Exotoxin , Gene , Genetic material , HIV , HIV-1 , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Immunity , Immunization , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Neurotoxin , Pathogenesis , Phenotype , Plasmacytoid dendritic cell , Signal transduction , Signaling , Signaling cascade , Signalling , Therapeutic , Toxin , Treatment , Variolation , Viral replication , Virulence , Virus Title: Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus. PMID: 16533886 Related Articles Authors: Draenert, R , Allen, T M , Liu, Y , Wrin, T , Chappey, C , Verrill, C L , Sirera, G , Eldridge, R L , Lahaie, M P , Ruiz, L , Clotet, B G , Petropoulos, C J , Walker, B D , Martnez-Picado, J Journal: J Exp Med , Vol. 203 (3): 529-39 , 2006 Abstract: The predictability of virus-host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection , 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape . Affiliation: Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA . Pubmed MeSH: Amino Acid Substitution , Antibodies, Viral , CD8-Positive T-Lymphocytes , Epitopes, T-Lymphocyte , Evolution, Molecular , Follow-Up Studies , Gene Products, env , HIV Seropositivity , Humans , Immunity, Cellular , Point Mutation Wikipedia: AIDS Virus , Adult , Animal virus , Antibodies , Antigenic determinants , Cell count , Cistron , Environment , Environmental Impact , Environmental Policy , Environmental impacts , Epitopes , Evolution , Gene , Genetic diversity , Genetic material , Genetic variation , HIV , HIV-1 , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Humoral immunity , Immunity , Immunization , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Mutation , T-Cell , T-lymphocyte , T Lymphocytes , T cells , Variation (genetics) , Variolation , Viral burden , Viral load , Virus Title: Suppression of HIV-1 viral replication and cellular pathogenesis by a novel p38 / JNK kinase inhibitor. PMID: 15075508 Related Articles Authors: Muthumani, K , Wadsworth, S A , Dayes, N S , Hwang, D S , Choo, A Y , Abeysinghe, H R , Siekierka, J J , Weiner, D B Journal: AIDS , Vol. 18 (5): 739-48 , 2004 Abstract: OBJECTIVE: To analyze a novel compound, which inhibits serine-threonine protein kinase p38 , for its possible bioactivity against HIV-1 infection . METHODS: Proteins involved in cellular signal transduction pathways represent a novel class of host therapeutic targets for infectious diseases . In this regard the serine/threonine kinase p38 MAPK , a member of the mitogen-activated protein ( MAP ) kinase superfamily of signal transduction molecules may play an important role in HIV-1 infection . We analyzed the ability of this compound (RWJ67657) to inhibit HIV replication in primary T cells and monocytes. Cellular expression of phospho- p38MAPK was studied by Western blot analysis. Blockade of HIV infection induced apoptosis was measured by Annexin V staining. RESULTS: p38 inhibitor RWJ67657 was effective in inhibiting HIV-1 replication in both T-cell and monocyte cell lines, irrespective of the coreceptor used by the virus for entry into the cell. Importantly, both reverse transcriptase and protease resistant escape mutant viruses were effectively suppressed by RWJ67657. In addition, the tested compounds block HIV-induced T-cell apoptosis, a critical means of T-cell depletion linked to AIDS progression. CONCLUSION: Several steps in the HIV-1 virus life cycle appear to depend on cellular activation, including activation of the p38 pathway. Without activation virus replication is thought to be blocked due to incomplete reverse transcription and a lack of proviral DNA integration. The data collectively illustrate that inhibition of the p38 pathway can affect HIV-1 replication. Interruption of HIV infection by p38 inhibitors underscores the value of exploring antiviral drugs that target host cellular proteins. Affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia , Pennsylvania 19104, USA . Pubmed MeSH: Analysis of Variance , Biological Markers , Drug Resistance, Viral , Humans , Imidazoles , Jurkat Cells , Phosphorylation , Pyridines , U937 Cells , p38 Mitogen-Activated Protein Kinases Wikipedia: AIDS , AIDS Virus , Acquired Immune Deficiency Syndrome , Acquired Immunodeficiency Syndrome , Animal virus , Annexin A5 , Annexin V , Annexins , Antiviral agents , Antiviral drugs , Antivirals , Apoptosis , B-DNA , Blotting, western , Cell line , Communicable disease , DNA , DNA-directed RNA polymerase , Deoxyribonucleic Acid , Drug delivery systems , Drugs , HIV , HIV-1 , HIV infection , HTLV-III , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Infectious Disease , Kinase , Life cycle , Lipocortin , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Mitogen-activated protein kinases , Monocyte , Peptide hydrolases , Phosphotransferases , Proteases , Protein-serine-threonine kinases , Protein Kinase , Protein kinases , Proteins , RNA-directed DNA polymerase , RNA Polymerase , Reverse Transcriptase , Reverse transcription , Serine-threonine kinase , Serine kinase , Signal transduction , Signal transduction pathway , T-Cell , T-lymphocyte , T Lymphocytes , T cells , Therapeutic , Treatment , Virus , Western Blot , Western blotting The induction of Toll-like receptor tolerance enhances rather than suppresses HIV-1 gene expression in transgenic mice. PMID: 14657211 Related Articles Authors: Bfica, A , Scanga, C A , Equils, O , Sher, A Journal: J Leukoc Biol , Vol. 75 (3): 460-6 , 2004 Abstract: Microbial-induced proinflammatory pathways are thought to play a key role in the activation of human immunodeficiency virus type 1 ( HIV-1 ) gene expression. The induction of Toll-like receptor ( TLR ) tolerance leads to a complex reprogramming in the pattern of inflammatory gene expression and down-modulates tumor necrosis factor alpha ( TNF-alpha ), interleukin (IL)-1, and IL-6 production. Using transgenic (Tg) mice that incorporate the entire HIV-1 genome, including the long-terminal repeat, we have previously demonstrated that a number of different TLR ligands induce HIV-1 gene expression in cultured splenocytes as well as purified antigen-presenting cell populations. Here, we have used this model to determine the effect of TLR -mediated tolerance as an approach to inhibiting microbial-induced viral gene expression in vivo. Unexpectedly, Tg splenocytes and macrophages, rendered tolerant in vitro to TLR2 , TLR4 , and TLR9 ligands as assessed by proinflammatory cytokine secretion and nuclear factor-kappaB activation, showed enhanced HIV-1 p24 production. A similar enhancement was observed in splenocytes tolerized and then challenged with heterologous TLR ligands. Moreover, TLR2 - and TLR4 -homotolerized mice demonstrated significantly increased plasma p24 production in vivo despite lower levels of TNF-alpha . Together, these results demonstrate that HIV-1 expression is enhanced in TLR -reprogrammed host cells, possibly reflecting a mechanism used by the virus to escape the effects of microbial-induced tolerance during natural infection in vivo. Affiliation: Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda , MD 20982, USA . abafica@niaid.nih.gov Pubmed MeSH: Animals , Cysteine , Drug Tolerance , Gene Expression Regulation , Gene Expression Regulation, Viral , HIV Core Protein p24 , Immune Tolerance , Inflammation , Lipopolysaccharides , Lipoproteins , Membrane Glycoproteins , Receptors, Cell Surface , Toll-Like Receptor 2 , Toll-Like Receptor 4 Wikipedia: AIDS Virus , Animal virus , Antigen-presenting cell , Antigen presenting cells , Benign neoplasm , Binding , Cachectin , Cancer , Cistron , Cytokine , Gene , Gene Expression , Genetic material , Genome , Genomics , HIV , HIV-1 , HTLV-III , Host cell , House Mouse , House mice , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , IL-6 , IL6 , Interleukin , Interleukin-6 , Interleukin 6 , Laboratory mice , Laboratory mouse , Ligand , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Macrophage , Mice , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Nature , Necrosis , Neoplasm , Programmed cell death , TNF , TNF-alpha , TNF alpha , Toll-like receptor , Toll like receptor , Transgene , Tumor , Tumor Necrosis Factor , Tumor necrosis factor-alpha , Tumor necrosis factor alpha , Tumor necrosis factors , Virus Title: Human immunodeficiency virus type 1 Nef functions at the level of virus entry by enhancing cytoplasmic delivery of virions. PMID: 11222724 Related Articles Authors: Schffer, E , Geleziunas, R , Greene, W C Journal: J Virol , Vol. 75 (6): 2993-3000 , 2001 Abstract: The Nef protein of the type 1 human immunodeficiency virus ( HIV-1 ) plays a key although poorly understood role in accelerating the progression of clinical disease in vivo. Nef exerts several biological effects in vitro, including enhancement of virion infectivity, downregulation of CD4 and major histocompatibility complex class I receptor expression, and modulation of various intracellular signaling pathways . The positive effect of Nef on virion infectivity requires its expression in the producer cell, although its effect is manifested in the subsequent target cell of infection . Prior studies suggest that Nef does not alter viral entry into target cells; nevertheless, it enhances proviral DNA synthesis, arguing for an action of Nef at the level of viral uncoating or reverse transcription. However, these early studies discounting an effect of Nef on virion entry may be confounded by the recent finding that HIV enters cells by both fusion and endocytosis. Using epifluorescence microscopy to monitor green fluorescent protein-Vpr -labeled HIV virion entry into HeLa cells, we find that endocytosis forms a very active pathway for virus uptake. Virions entering via the endocytic pathway do not support productive infection of the host cell, presumably reflecting their inability to escape from the endosomes. Conversely, our studies now demonstrate that HIV Nef significantly enhances CD4- and chemokine receptor-dependent entry of HIV virions into the cytoplasmic compartment of target cells. Mutations in Nef either impairing its ability to downregulate CD4 or disrupting its polyproline helix compromise virion entry into the cytoplasm. We conclude that Nef acts at least in part as a regulator of cytosolic viral entry and that this action contributes to its positive effects on viral infectivity. Affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco , California 94141, USA . Pubmed MeSH: Antigens, CD4 , Gene Products, vpr , Green Fluorescent Proteins , Humans , Luminescent Proteins , Virus Replication , nef Gene Products, Human Immunodeficiency Virus , vpr Gene Products, Human Immunodeficiency Virus Wikipedia: AIDS Virus , Acceleration , Animal virus , B-DNA , Chemokines , Cytoplasm , Cytosol , DNA , DNA Replication , DNA synthesis , Deoxyribonucleic Acid , Down-regulation , Downregulation , Endocytosis , Endosome , Enteritis , Fluorescence , HIV , HIV-1 , HTLV-III , HeLa cell , Histocompatibility , Host cell , Human Immunodeficiency Virus , Human immunodeficiency virus 1 , Intracellular , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , MHC Class I , Major Histocompatibility Complex , Microscopy , Mutation , Nef gene product , Proteins , Protoplasm , Receptor down-regulation , Reverse transcription , Signal transduction , Signaling , Signaling cascade , Signalling , T cell receptor , Virion , Virus Title: Antiviral pressure exerted by HIV-1 -specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. PMID: 9018240 Related Articles Authors: Borrow, P , Lewicki, H A , Wei, X Q , Horwitz, M S , Peffer, N , Meyers, H L , Nelson, J A , Gairin, J E , Hahn, B H , Oldstone, M B , Shaw, G M Journal: Nat Med , Vol. 3 (2): 205-11 , 1997 Abstract: The HIV-1 -specific cytotoxic T lymphocyte (CTL) response is temporally associated with the decline in viremia during primary HIV-1 infection , but definitive evidence that it is of importance in virus containment has been lacking. Here we show that in a patient whose early CTL response was focused on a highly immunodominant epitope in gp 160 , there was rapid elimination of the transmitted virus strain and selection for a virus population bearing amino acid changes at a single residue within this epitope, which conferred escape from recognition by epitope-specific CTL. The magnitude ( 100-fold), kinetics (30-72 days from onset of symptoms) and genetic pathways of virus escape from CTL pressure were comparable to virus escape from antiretroviral therapy, indicating the biological significance of the CTL response in vivo. One aim of HIV-1 vaccines should thus be to elicit strong CTL responses against multiple codominant viral epitopes. Affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA . Pubmed MeSH: Acquired Immunodeficiency Syndrome , HIV Envelope Protein gp160 , Humans , Oligonucleotide Probes Wikipedia: Active immunization , Amino Acids , Animal virus , Antigenic determinants , Antiviral agents , Antiviral drugs , Antivirals , Client , Cytotoxic T-lymphocyte , Cytotoxic T lymphocytes , Epitopes , HIV-1 , Human immunodeficiency virus 1 , Kinetic , Lymphocyte , Patient , Pressure , T-Cell , T-lymphocyte , T-lymphocytes, cytotoxic , T Lymphocytes , T cells , Vaccination , Vaccines , Viremia , Virus Title: T helper cell activation and human retroviral pathogenesis. PMID: 8987361 Related Articles Authors: Copeland, K F , Heeney, J L Journal: Microbiol Rev , Vol. 60 (4): 722-42 , 1996 Abstract: T helper (Th) cells are of central importance in regulating many critical immune effector mechanisms. The profile of cytokines produced by Th cells correlates with the type of effector cells induced during the immune response to foreign antigen. Th1 cells induce the cell-mediated immune response, while Th2 cells drive antibody production. Th cells are the preferential targets of human retroviruses. Infections with human T-cell leukemia virus (HTLV) or human immunodeficiency virus ( HIV ) result in the expansion of Th cells by the action of HTLV ( adult T-cell leukemia ) or the progressive loss of T cells by the action of HIV (AIDS). Both retrovirus infections impart a high-level activation state in the host immune cells as well as systemically. However, diverging responses to this activation state have contrasting effects on the Th-cell population. In HIV infection , Th-cell loss has been attributed to several mechanisms, including a selective elimination of cells by apoptosis. The induction of apoptosis in HIV infection is complex, with many different pathways able to induce cell death. In contrast, infection of Th cells with HTLV-1 affords the cell a protective advantage against apoptosis. This advantage may allow the cell to escape immune surveillance, providing the opportunity for the development of Th-cell cancer. In this review, we will discuss the impact of Th-cell activation and general immune activation on human retrovirus expression with a focus upon Th-cell function and the progression to disease. Affiliation: Department of Pathology, McMaster University, Hamilton , Ontario , Canada . copelndk@fhs.mcmaster.ca Pubmed MeSH: Acquired Immunodeficiency Syndrome , Deltaretrovirus Infections , Disease Progression , HIV-1 , Humans , Immune Tolerance , Lymphocyte Activation , Viral Proteins Wikipedia: AIDS Virus , ATLL , ATLV , Active immunity , Adult , Adult T-cell leukemia , Alien , Animal virus , Antibodies , Antigen , Apoptosis , Azidothymidine , Cell-mediated immunity , Cell death , Cell mediated immunity , Cellular immunity , Cytokinesis , Emigrant , Foreigner , HIV , HIV infection , HTLV-1 , HTLV-I , HTLV-III , Helper T-cell , Helper T cells , Helper cell , Human Immunodeficiency Virus , Human t-lymphotropic virus 1 , Humoral immunity , Immigrant , Immunity , Immunity, cellular , Immunization , Leukemia , Leukemia, t-cell , Lymphadenopathy-Associated Virus , Lymphadenopathy Associated Virus , Oncovirus , Retrovir , Retroviridae , Retroviridae infections , Retrovirus , T-ALL , T-Cell , T-cell leukemia , T-lymphocyte , T-lymphocytes, helper-inducer , T Lymphocytes , T cells , Th1 cell , Th2 cell , Variolation , Virus , Zidovudine

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