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研究揭示SIV和HIV重激活机制
2020-01-27 14:37

近日,美国埃默里大学Guido Silvestri及其研究组发现,N-803与CD8+细胞耗竭可强效且持续性激活SIV和HIV。相关论文于2020年1月22日在线发表于《自然》杂志。

研究人员表示,人类免疫缺陷病毒(HIV)在接受抗逆转录病毒疗法(ART)的HIV个体中无限期地持续存在,这是由于其潜伏感染细胞中含有复制型病毒。
 
为了更好地了解造成潜伏期持续和逆转的机制,研究人员将白介素15超级激动剂N-803与CD8+淋巴细胞耗竭一起在经猿猴免疫缺陷病毒(SIV)感染的ART治疗的猕猴中使用。尽管只用N-803不能重新激活病毒的产生,但在CD8+淋巴细胞耗尽后与ART治疗结合使用,可以在体内引起病毒的持续强效激活。
 
研究人员发现在所有猕猴中,每毫升病毒血中超过60个拷贝(n=14; 100%),并且在N-803给药后每周收集的56个样本(73.2%)中,有41个病毒血症。值得注意的是,在接受ART治疗的HIV感染人源化小鼠中获得了一致的结果。此外,研究人员观察到与CD8+T细胞共培养可阻断N-803对潜伏感染HIV原代人CD4+T细胞体外潜伏期的逆转作用。这些结果使人们进一步了解了ART抑制感染期间引起潜伏期逆转和慢病毒重新激活的机制。
 
附:英文原文

Title: Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8 + cells

Author: Julia Bergild McBrien, Maud Mavigner, Lavinia Franchitti, S. Abigail Smith, Erick White, Gregory K. Tharp, Hasse Walum, Kathleen Busman-Suhay, Christian R. Aguilera-Sandoval, William O. Thayer, Rae Ann Spagnuolo, Martina Kovarova, Angela Wahl, Barbara Cervasi, David M. Margolis, Thomas H. Vanderford, Diane G. Carnathan, Mirko Paiardini, Jeffrey D. Lifson, John H. Lee, Jeffrey T. Safrit, Steven E. Bosinger, Jacob D. Estes, Cynthia A. Derdeyn, J. Victor Garcia, Deanna A. Kulpa, Ann Chahroudi, Guido Silvestri

Issue&Volume: 2020-01-22

Abstract: Human immunodeficiency virus (HIV) persists indefinitely in individuals with HIV who receive antiretroviral therapy (ART) owing to a reservoir of latently infected cells that contain replication-competent virus1,2,3,4. Here, to better understand the mechanisms responsible for latency persistence and reversal, we used the interleukin-15 superagonist N-803 in conjunction with the depletion of CD8+ lymphocytes in ART-treated macaques infected with simian immunodeficiency virus (SIV). Although N-803 alone did not reactivate virus production, its administration after the depletion of CD8+ lymphocytes in conjunction with ART treatment induced robust and persistent reactivation of the virus in vivo. We found viraemia of more than 60 copies per ml in all macaques (n = 14; 100%) and in 41 out of a total of 56 samples (73.2%) that were collected each week after N-803 administration. Notably, concordant results were obtained in ART-treated HIV-infected humanized mice. In addition, we observed that co-culture with CD8+ T cells blocked the in vitro latency-reversing effect of N-803 on primary human CD4+ T cells that were latently infected with HIV. These results advance our understanding of the mechanisms responsible for latency reversal and lentivirus reactivation during ART-suppressed infection.

DOI: 10.1038/s41586-020-1946-0

Source: https://www.nature.com/articles/s41586-020-1946-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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