Membrane-assisted assembly and selective secretory autophagy of enteroviruses.
Membrane-assisted assembly and selective secretory autophagy of enteroviruses.
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DOI：
10.1038/s41467-022-33483-7
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发表时间：
2022-10-10
影响因子：
16.6
通讯作者：
Carlson, Lars-Anders
中科院分区：
文献类型：
--
作者：
Dahmane, Selma;Kerviel, Adeline;Morado, Dustin R.;Shankar, Kasturika;Ahlman, Bjorn;Lazarou, Michael;Altan-Bonnet, Nihal;Carlson, Lars-Anders
肠道病毒是一种无包膜的正义RNA病毒，可引起人类多种疾病。它们的快速繁殖依赖于细胞质膜的重塑以进行病毒基因组复制。目前尚不清楚病毒粒子如何围绕这些新合成的基因组组装，以及它们如何然后装载到自噬膜中以通过分泌性自噬释放。在这里，我们使用受感染细胞的冷冻电子断层扫描显示脊髓灰质炎病毒直接在复制膜上组装。衣壳从膜上的药理学解栓消除了RNA的结合。我们的数据直接将膜结合的半衣壳可视化为突出的病毒体组装中间体。组装进程通过这个中间体取决于III类磷脂酰肌醇3-激酶VPS 34，一个关键的宿主细胞自噬因子。另一方面，经典的自噬引发剂ULK 1被证明可以限制病毒粒子的产生，因为它的抑制会导致病毒粒子在大量细胞内阵列中的积累增加，然后在稍后的时间点增加囊泡释放。最后，我们确定了病毒诱导的自噬中的多层选择性，对空衣壳的RNA负载病毒粒子的强烈选择以及病毒粒子与其他类型的自噬体内容物的分离。这些发现为脊髓灰质炎病毒生命周期的多个阶段提供了一个综合结构框架。肠道病毒是无包膜的正义RNA病毒，其调节细胞质膜以进行复制。为了揭示肠道病毒如何在新生RNA基因组周围组装并包装成自噬体释放，Dahmane等人对脊髓灰质炎病毒感染的细胞进行了冷冻电子断层扫描。他们发现组装中间体仅存在于复制区室的胞质侧，并提供了宿主因子VPS 34参与组装中间体进展的证据。
Enteroviruses are non-enveloped positive-sense RNA viruses that cause diverse diseases in humans. Their rapid multiplication depends on remodeling of cytoplasmic membranes for viral genome replication. It is unknown how virions assemble around these newly synthesized genomes and how they are then loaded into autophagic membranes for release through secretory autophagy. Here, we use cryo-electron tomography of infected cells to show that poliovirus assembles directly on replication membranes. Pharmacological untethering of capsids from membranes abrogates RNA encapsidation. Our data directly visualize a membrane-bound half-capsid as a prominent virion assembly intermediate. Assembly progression past this intermediate depends on the class III phosphatidylinositol 3-kinase VPS34, a key host-cell autophagy factor. On the other hand, the canonical autophagy initiator ULK1 is shown to restrict virion production since its inhibition leads to increased accumulation of virions in vast intracellular arrays, followed by an increased vesicular release at later time points. Finally, we identify multiple layers of selectivity in virus-induced autophagy, with a strong selection for RNA-loaded virions over empty capsids and the segregation of virions from other types of autophagosome contents. These findings provide an integrated structural framework for multiple stages of the poliovirus life cycle. Enteroviruses are non-enveloped positive-sense RNA viruses that modulate cytoplasmic membranes for replication. To enlighten how enteroviruses assemble around nascent RNA genomes and get package into autophagosomes for release, Dahmane et al. perform cryo-electron tomography of poliovirus-infected cells. They find assembly intermediates that are only present on the cytosolic side of the replication compartment and provide evidence that host factor VPS34 is involved in progression of assembly intermediates.
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影响因子：
64.8
作者：
Feng Z;Hensley L;McKnight KL;Hu F;Madden V;Ping L;Jeong SH;Walker C;Lanford RE;Lemon SM
通讯作者：
Lemon SM
影响因子：
5.9
作者：
Jackson, William T.
通讯作者：
Jackson, William T.
影响因子：
8
作者：
BASAVAPPA, R;SYED, R;HOGLE, JM
通讯作者：
HOGLE, JM
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
21.3
作者：
Gatica D;Lahiri V;Klionsky DJ
通讯作者：
Klionsky DJ