Data_Sheet_1_VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses.ZIP

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.

进化保守的AAA+ ATP酶含缬酪肽蛋白（valosin-containing protein, VCP）此前被证实为多个病毒科病毒的促病毒宿主因子，涉及的病毒科包括黄病毒科（Flaviviridae）、小RNA病毒科（Picornaviridae）以及疱疹病毒科（Herpesviridae）。已有研究显示，VCP可调控辛德毕斯病毒受体的转运过程，并作为赛姆利基森林病毒（Semliki Forest virus, SFV）复制酶区室的组分之一发挥功能。然而，在包括基孔肯雅病毒（chikungunya virus, CHIKV）在内的甲病毒属病毒的复制过程中，该细胞蛋白的功能尚未得到系统评估。本研究借助小干扰RNA（siRNA）、化学抑制剂与反式复制试验，证实VCP是参与基孔肯雅病毒复制的促病毒宿主因子。免疫荧光试验证实，VCP可与非结构复制酶蛋白发生共定位，但未与双链RNA灶（dsRNA foci）共定位，这一现象可能源于VCP表位的不可及性。在不同人类细胞系中，奥永翁病毒（o’nyong’nyong virus, ONNV）与赛姆利基森林病毒等其他甲病毒也表现出依赖VCP的促病毒作用。VCP在多个病毒科中具备促病毒功能的结论，现已拓展至甲病毒属的基孔肯雅病毒与奥永翁病毒的复制过程，这进一步凸显了VCP在病毒-宿主互作生物学中的核心地位。