小柯机器人

美国西南医学中心John W. Schoggins课题组发现，TRIM7抑制肠病毒复制并促进致病性更强的病毒变体出现。相关论文于2021年5月31日在线发表在《细胞》杂志上。

研究人员发现，E3泛素连接酶TRIM7是一种细胞内在抗病毒效应器，其通过靶向病毒2BC（一种膜重塑蛋白质）来进行泛素化和蛋白酶体依赖性降解。通过TRIM7施加的选择性压力导致在病毒2C ATP酶/螺旋酶中具有单点突变的TRIM7抗性柯萨奇病毒出现。在培养的细胞中，突变有助于病毒逃逸TRIM7，但损害了最佳的病毒复制效率，并且这种与过度活跃和结构可塑的2C ATP酶相关联。

出乎意料的是，TRIM7抗性病毒在小鼠中具有复制优势，并导致致命的胰腺炎。这些发现揭示了一种靶向肠道病毒复制的独特机制，并提供了宿主限制因子如何促进病毒演化的新见解。

据了解，为了控制病毒感染，脊椎动物依赖于诱导的干扰素反应和较少表征的细胞内在反应，这由“已就绪”的抗病毒效应蛋白组成。

附：英文原文

Title: TRIM7 inhibits enterovirus replication and promotes emergence of a viral variant with increased pathogenicity

Author: Wenchun Fan, Katrina B. Mar, Levent Sari, Ilona K. Gaszek, Qiang Cheng, Bret M. Evers, John M. Shelton, Mary Wight-Carter, Daniel J. Siegwart, Milo M. Lin, John W. Schoggins

Issue&Volume: 2021-05-31

Abstract: To control viral infection, vertebrates rely on both inducible interferon responsesand less well-characterized cell-intrinsic responses composed of “at the ready” antiviraleffector proteins. Here, we show that E3 ubiquitin ligase TRIM7 is a cell-intrinsicantiviral effector that restricts multiple human enteroviruses by targeting viral2BC, a membrane remodeling protein, for ubiquitination and proteasome-dependent degradation.Selective pressure exerted by TRIM7 results in emergence of a TRIM7-resistant coxsackieviruswith a single point mutation in the viral 2C ATPase/helicase. In cultured cells, themutation helps the virus evade TRIM7 but impairs optimal viral replication, and thiscorrelates with a hyperactive and structurally plastic 2C ATPase. Unexpectedly, theTRIM7-resistant virus has a replication advantage in mice and causes lethal pancreatitis.These findings reveal a unique mechanism for targeting enterovirus replication andprovide molecular insight into the benefits and trade-offs of viral evolution imposedby a host restriction factor.

DOI: 10.1016/j.cell.2021.04.047

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00582-1