ESCRT machinery components are required for Orthobunyavirus particle production in Golgi compartments.
ESCRT machinery components are required for Orthobunyavirus particle production in Golgi compartments.
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DOI：
10.1371/journal.ppat.1007047
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发表时间：
2018-05
期刊：
影响因子：
6.7
通讯作者：
daSilva LLP
中科院分区：
文献类型：
--
作者：
Barbosa NS;Mendonça LR;Dias MVS;Pontelli MC;da Silva EZM;Criado MF;da Silva-Januário ME;Schindler M;Jamur MC;Oliver C;Arruda E;daSilva LLP
Peribunyaviridae 是一个 RNA 病毒大家族，有多个成员，可引起人类和牲畜轻度至重度疾病。尽管它们在公共卫生中很重要，但人们对这些病毒劫持的宿主细胞因子支持组装和细胞流出的了解却很少。在这里，我们展示了奥罗普切病毒（Oropoouche 病毒）的组装，该病毒是正布尼亚病毒属的成员，在南美洲国家引起频繁的虫媒病毒感染，涉及病毒颗粒向高尔基池腔出芽。随着病毒复制的进行，这些高尔基体亚室变大，并与高尔基体堆叠物理分离，形成奥罗普切病毒工厂 (Vfs) 单位。在超微结构水平上，这些病毒修饰的高尔基体获得了 MVB 外观，虽然它们缺乏典型的早期和晚期内体标记，但它们富含参与 MVB 生物发生的转运所需的内体复合物 (ESCRT) 蛋白。进一步的显微镜和病毒复制分析表明，有效的 Vf 形态发生和感染性 OROV 颗粒的产生需要功能性 ESCRT 机制。综上所述，我们的结果表明，OROV 将 ESCRT 机械组件吸引到高尔基体池，以介导病毒在这些区室组装和出芽所需的膜重塑事件。这代表了病毒如何劫持宿主细胞成分以协调形态发生的前所未有的机制。周围布尼亚病毒科是RNA病毒的一个大目，分布于全球，可能引起人类疾病。在这项研究中，我们分析了奥罗普切病毒（OROV）的组装途径，奥罗普切病毒是正布尼亚病毒属的一种周围布尼亚病毒，是拉丁美洲国家常见的节肢动物传播病毒性疾病的病原体。 OROV 具有嗜神经性，会引起使人衰弱的发热性疾病，在某些患者中可能会发展为脑膜炎和/或脑炎。我们表明，OROV 的组装涉及病毒颗粒向高尔基池内腔出芽。在此过程中，运输所需的内体分选复合物 (ESCRT) 成分被劫持到高尔基体膜，参与病毒工厂的形态发生，并且是有效释放感染性 OROV 颗粒所必需的。尽管许多包膜病毒已经进化到侵占 ESCRT 机器的元件来进行组装和出芽，但数据提供了前所未有的证据，表明 ESCRT 蛋白可能在病毒复制过程中重新定位到高尔基体区室，并且该机器是正布尼亚病毒的组装/排出所必需的。
Peribunyaviridae is a large family of RNA viruses with several members that cause mild to severe diseases in humans and livestock. Despite their importance in public heath very little is known about the host cell factors hijacked by these viruses to support assembly and cell egress. Here we show that assembly of Oropouche virus, a member of the genus Orthobunyavirus that causes a frequent arboviral infection in South America countries, involves budding of virus particles toward the lumen of Golgi cisternae. As viral replication progresses, these Golgi subcompartments become enlarged and physically separated from Golgi stacks, forming Oropouche viral factory (Vfs) units. At the ultrastructural level, these virally modified Golgi cisternae acquire an MVB appearance, and while they lack typical early and late endosome markers, they become enriched in endosomal complex required for transport (ESCRT) proteins that are involved in MVB biogenesis. Further microscopy and viral replication analysis showed that functional ESCRT machinery is required for efficient Vf morphogenesis and production of infectious OROV particles. Taken together, our results indicate that OROV attracts ESCRT machinery components to Golgi cisternae to mediate membrane remodeling events required for viral assembly and budding at these compartments. This represents an unprecedented mechanism of how viruses hijack host cell components for coordinated morphogenesis. The Peribunyaviridae is a large order of RNA viruses that are globally distributed and may cause human diseases. In this study, we analyzed the assembly pathway of Oropouche virus (OROV), a peribunyavirus of the orthobunyavirus genus that is the etiologic agent of a frequent arthropod-transmitted viral disease in Latin American countries. OROV is neurotropic and causes a debilitating febrile illness, which can progress to meningitis and/or encephalitis in some patients. We show that assembly of OROV involves budding of virus particles toward the lumen of Golgi cisternae. During this process, endosomal sorting complex required for transport (ESCRT) components are hijacked to Golgi membranes to participate in the morphogenesis of viral factories and are required for efficient release of infectious OROV particles. Although many enveloped viruses have evolved to usurp elements of the ESCRT machinery for assembly and budding, the data provides unprecedented evidence that ESCRT proteins may be relocated to Golgi compartments during viral replication, and that this machinery is required for assembly/egress of an Orthobunyavirus.
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DOI：
10.1038/nrm2937
发表时间：
2010-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Koreishi M;Gniadek TJ;Yu S;Masuda J;Honjo Y;Satoh A
通讯作者：
Satoh A
影响因子：
3.3
作者：
Bishop, N;Woodmane, P
通讯作者：
Woodmane, P
影响因子：
3.7
作者：
Ariumi Y;Kuroki M;Maki M;Ikeda M;Dansako H;Wakita T;Kato N
通讯作者：
Kato N
影响因子：
3.7
作者：
Ku PI;Bendjennat M;Ballew J;Landesman MB;Saffarian S
通讯作者：
Saffarian S