Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway.
Nipah Virus C Protein Recruits Tsg101 to Promote the Efficient Release of Virus in an ESCRT-Dependent Pathway.
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DOI：
10.1371/journal.ppat.1005659
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发表时间：
2016-05
期刊：
影响因子：
6.7
通讯作者：
Lee B
中科院分区：
文献类型：
--
作者：
Park A;Yun T;Vigant F;Pernet O;Won ST;Dawes BE;Bartkowski W;Freiberg AN;Lee B
尼帕病毒是副粘病毒科亨尼帕病毒属的致命成员，其出芽被认为不依赖于宿主ESCRT途径，该途径对于许多包膜病毒的出芽至关重要。这一结论是基于在不存在其他病毒组分的情况下病毒基质蛋白的出芽特性。在这里，我们发现，病毒C蛋白，这是以前研究其在先天免疫拮抗作用，招募ESCRT途径，以促进有效的病毒释放。ESCRT的抑制或ESCRT因子Tsg 101的耗竭消除了C对基质出芽的增强作用，并损害了活尼帕病毒的释放。此外，尽管已知的亨尼帕病毒的C蛋白的低序列同源性，但它们都增强了其同源基质蛋白的出芽，表明亨尼帕病毒C蛋白的保守和先前未知的功能。尼帕病毒是一种致命的病原体（40-100%死亡率），每年在东南亚爆发，由其天然果蝠水库的溢出造成。病毒C蛋白是仅有的九种病毒蛋白之一，但其在促进病毒复制中的作用尚未完全了解。在这里，我们发现C蛋白促进了Nipah病毒从感染细胞中的有效释放。它通过在宿主ESCRT复合物Tsg 101中招募一个必需因子来实现。ESCRT复合物在介导类似于病毒出芽的膜夹断事件中具有充分表征的功能。此外，我们发现，在同一属（亨尼帕病毒）的相关病毒的C蛋白也促进病毒出芽，这表明，以前未知的功能的亨尼帕病毒C蛋白是保守的。这项工作阐明了具有重大爆发和公共卫生问题的亨尼帕病毒的基本生物学，并为进一步的调查打开了大门。
The budding of Nipah virus, a deadly member of the Henipavirus genus within the Paramyxoviridae, has been thought to be independent of the host ESCRT pathway, which is critical for the budding of many enveloped viruses. This conclusion was based on the budding properties of the virus matrix protein in the absence of other virus components. Here, we find that the virus C protein, which was previously investigated for its role in antagonism of innate immunity, recruits the ESCRT pathway to promote efficient virus release. Inhibition of ESCRT or depletion of the ESCRT factor Tsg101 abrogates the C enhancement of matrix budding and impairs live Nipah virus release. Further, despite the low sequence homology of the C proteins of known henipaviruses, they all enhance the budding of their cognate matrix proteins, suggesting a conserved and previously unknown function for the henipavirus C proteins. Nipah virus is a deadly pathogen (40–100% mortality) that has yearly outbreaks in Southeast Asia, resulting from spillover from its natural fruit bat reservoir. The viral C protein is one of only nine virus proteins, but its role in promoting virus replication is not fully understood. Here, we found that the C protein promotes the efficient release of budding Nipah virus from infected cells. It does so by recruiting an essential factor in the host ESCRT complex, Tsg101. The ESCRT complex has well-characterized functions in mediating membrane pinching off events that resemble virus budding. Further, we found that the C proteins of related viruses within the same genus (Henipavirus) also promote virus budding, suggesting that this previously unknown function of the henipavirus C proteins is conserved. This work illuminates the basic biology of henipaviruses with significant outbreak and public health concern, and opens the door to further lines of inquiry.