VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses
VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses
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DOI：
10.3389/fmicb.2019.02236
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发表时间：
2019-09-24
影响因子：
5.2
通讯作者：
Ng, Lisa F. P.
中科院分区：
文献类型：
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作者：
Carissimo, Guillaume;Chan, Yi-Hao;Ng, Lisa F. P.
进化上保守的AAA+ ATP酶valosin-containing蛋白（VCP）先前被证明是来自不同病毒科的几种病毒的前病毒宿主因子，如黄病毒科、小核糖核酸病毒科和疱疹病毒科。VCP被证明影响辛德毕斯病毒受体的运输，并作为塞姆利基森林病毒（SFV）复制酶区室的组成部分发挥作用。然而，在包括基孔肯雅病毒（CHIKV）在内的甲病毒复制期间，没有评估这种细胞蛋白的作用。使用siRNA，化学抑制剂和反式复制测定，我们在这里表明，VCP是一种参与CHIKV复制的前病毒因子。免疫荧光分析证实，VCP与非结构复制酶蛋白共定位，但不与dsRNA焦点可能是由于VCP表位不可用。在不同的人类细胞系中，也观察到VCP对其他甲病毒如奥宁宁病毒（ONNV）和SFV的前病毒作用。VCP前病毒在几个病毒家族中的作用现在扩展到甲病毒CHIKV和ONNV的复制，强调了VCP在病毒-宿主相互作用生物学中的关键作用。
The evolutionarily conserved AAA+ ATPase valosin-containing protein (VCP) was previously shown to be a proviral host factor for several viruses from different viral families such as Flaviviridae, Picornaviridae, and Herpesviridae. VCP was shown to affect trafficking of Sindbis virus receptor and functions as a component of Semliki Forest virus (SFV) replicase compartment. However, the role of this cellular protein was not evaluated during replication of alphaviruses including chikungunya virus (CHIKV). Using siRNA, chemical inhibitors, and trans-replication assays, we show here that VCP is a proviral factor involved in the replication of CHIKV. Immunofluorescence assays confirmed that VCP co-localized with non-structural replicase proteins but not with dsRNA foci possibly due to VCP epitope unavailability. VCP pro-viral role is also observed with other alphaviruses such as o'nyong'nyong virus (ONNV) and SFV in different human cell lines. VCP proviral roles on several viral families now extend to replication of alphaviruses CHIKV and ONNV, emphasizing the pivotal role of VCP in virus-host interaction biology.