Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress

Vaccinia virus hijacks ESCRT-mediated multivesicular body formation for virus egress
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痘苗病毒劫持 ESCRT 介导的多泡体形成以进行病毒出口

DOI:
10.1101/2020.07.15.203935
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发表时间:
2020
期刊:
--
影响因子:
--
通讯作者:
Huttunen M
Huttunen M
中科院分区:
--
文献类型:
--
作者:
Huttunen M

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痘病毒逃逸是一个复杂的过程,其中细胞质单膜结合的病毒粒子被包裹在细胞衍生的双膜中。这些三层膜颗粒,称为细胞内包膜病毒体(IEV),通过融合从感染细胞中释放。虽然包裹双膜被认为是来自病毒修饰的反式高尔基体或早期内体池,调节病毒包裹的细胞因子仍然在很大程度上不确定。为了鉴定该过程所需的细胞因子,对原型痘病毒、牛痘病毒(VACV)进行针对细胞膜运输蛋白的RNAi筛选。专注于运输所需的内体分选复合物(ESCRT),我们证明了ESCRT-III和VPS 4是将病毒包装成多泡体(MVB)所必需的。基于EM的MVB-IEV表征表明,它们占IEV产量的一半,表明MVB是VACV包裹膜的第二大来源。这些数据支持一种模型,即除了基于脑池的包裹外,VACV还劫持ESCRT介导的MVB形成以促进病毒外出和传播。
Poxvirus egress is a complex process whereby cytoplasmic single membrane–bound virions are wrapped in a cell-derived double membrane. These triple-membrane particles, termed intracellular enveloped virions (IEVs), are released from infected cells by fusion. Whereas the wrapping double membrane is thought to be derived from virus-modified trans-Golgi or early endosomal cisternae, the cellular factors that regulate virus wrapping remain largely undefined. To identify cell factors required for this process the prototypic poxvirus, vaccinia virus (VACV), was subjected to an RNAi screen directed against cellular membrane-trafficking proteins. Focusing on the endosomal sorting complexes required for transport (ESCRT), we demonstrate that ESCRT-III and VPS4 are required for packaging of virus into multivesicular bodies (MVBs). EM-based characterization of MVB-IEVs showed that they account for half of IEV production indicating that MVBs are a second major source of VACV wrapping membrane. These data support a model whereby, in addition to cisternae-based wrapping, VACV hijacks ESCRT-mediated MVB formation to facilitate virus egress and spread.
ESCRT 机器在细胞生物学和病毒复制中的功能不断增强。
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