Opportunistic intruders: how viruses orchestrate ER functions to infect cells.
Opportunistic intruders: how viruses orchestrate ER functions to infect cells.
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机会性入侵者：病毒如何编排ER功能以感染细胞。
DOI：
10.1038/nrmicro.2016.60
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Tsai B
中科院分区：
文献类型：
--
作者：
Ravindran MS;Bagchi P;Cunningham CN;Tsai B
病毒利用内质网（ER）的功能来促进其生命周期的早期和后期阶段，包括进入、翻译、复制、组装、形态发生和外出。这一观察揭示了病毒-宿主细胞关系的共同原则。病毒进入通常需要分解进入的病毒颗粒。这在多瘤病毒进入的情况下是最好的例证，其中ER相关的机器被劫持以分解病毒并促进进入胞质溶胶，从而进入细胞核。许多包膜病毒，如HIV和流感病毒，利用ER相关蛋白生物合成机制翻译其基因组并产生病毒颗粒形成所必需的结构蛋白和基因组复制过程中必不可少的非结构蛋白。病毒基因组的复制，特别是对于包括丙型肝炎病毒（HCV）、登革病毒（DENV）和西尼罗河病毒（WNV）的正义RNA（（+）RNA）病毒，发生在病毒诱导的膜结构中，所述膜结构最常来源于ER。这些结构的形成需要ER膜的形态学变化，涉及由靶向ER的病毒非结构蛋白诱导的膜重排。由于病毒组装通常与基因组复制偶联，因此组装过程通常依赖于ER膜。这种策略在RNA和DNA病毒中都可以看到。组装的病毒颗粒的形态发生也可以利用ER。这在无包膜轮状病毒中观察得最好，其瞬时包膜中间体在ER的内腔中转化为成熟和感染性颗粒。在ER中成熟后，子代病毒颗粒通过ER依赖性分泌途径排出宿主，这提供了通向细胞外环境的物理管道。ER积极促进病毒感染的所有步骤的总体观察结果具有治疗意义。选择性ER相关成分的化学抑制剂的开发正在成为抗病毒治疗的潜在途径，前提是这些抑制剂对宿主细胞具有最小的毒性。本文的在线版本（doi：10.1038/nrmicro.2016.60）包含补充材料，可供授权用户使用。许多宿主结构对于病毒感染至关重要，特别是内质网（ER）是必不可少的。在这篇综述中，Tsai和他的同事们强调了不同病毒颠覆ER的例子，以促进其生命周期的各个阶段，从入口到出口。本文的在线版本（doi：10.1038/nrmicro.2016.60）包含补充材料，可供授权用户使用。病毒破坏其宿主细胞的功能以复制并形成新的病毒后代。内质网（ER）被认为是控制病毒与宿主细胞内相互作用的中心细胞器。在这篇综述中，我们分析了来自不同家族的病毒如何在感染过程中聚集在这个独特的细胞内细胞器上，吸收了ER的一些内源性功能，以促进病毒生命周期从进入和复制到组装和出口的不同步骤。ER可以作为不同病毒家族感染过程中的共同点，从而提供了一个共同的原则，该原则是病毒和宿主细胞之间关系的明显复杂性的基础。由于大量的信息阐明了病毒-ER相互作用的分子和细胞基础，这些见解可能会导致关键治疗药物的开发。本文的在线版本（doi：10.1038/nrmicro.2016.60）包含补充材料，可供授权用户使用。
Viruses exploit the functions of the endoplasmic reticulum (ER) to promote both early and later stages of their life cycle, including entry, translation, replication, assembly, morphogenesis and egress. This observation reveals a shared principle that underlies virus–host cell relationships. Viral entry often requires disassembly of the incoming virus particle. This is best exemplified in the case of polyomavirus entry, in which ER-associated machineries are hijacked to disassemble the virus and promote entry to the cytosol en route to the nucleus. Many enveloped viruses, such as HIV and influenza virus, co-opt the ER-associated protein biosynthetic machinery to translate their genome and produce structural proteins that are necessary for the formation of virus particles and non-structural proteins that are essential during genome replication. Replication of the viral genome, particularly for positive-sense RNA ((+)RNA) viruses including hepatitis C virus (HCV), dengue virus (DENV) and West Nile virus (WNV), occurs in virus-induced membranous structures that are most often derived from the ER. The formation of these structures requires morphological changes to the ER membrane, involving membrane rearrangements that are induced by viral non-structural proteins that are targeted to the ER. As virus assembly is often coupled to genome replication, the assembly process frequently relies on the ER membrane. This strategy is seen for both RNA and DNA viruses. Morphogenesis of assembled virus particles can also take advantage of the ER. This is best observed in the non-enveloped rotavirus, for which a transient enveloped intermediate is converted to the mature and infectious particle in the lumen of the ER. After maturation in the ER, progeny virus particles egress the host through the ER-dependent secretory pathway, which provides a physical conduit to the extracellular environment. The overall observations that the ER actively promotes all steps of viral infection have therapeutic implications. The development of chemical inhibitors of selective ER-associated components is emerging as a potential avenue of antiviral therapy, provided that these inhibitors have minimal toxicity to the host cell. The online version of this article (doi:10.1038/nrmicro.2016.60) contains supplementary material, which is available to authorized users. Many host structures are vital for viral infection and the endoplasmic reticulum (ER), in particular, is essential. In this Review, Tsai and colleagues highlight examples of subversion of the ER by diverse viruses to promote all stages of their life cycle, from entry to egress. The online version of this article (doi:10.1038/nrmicro.2016.60) contains supplementary material, which is available to authorized users. Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents. The online version of this article (doi:10.1038/nrmicro.2016.60) contains supplementary material, which is available to authorized users.