Journal
VIRUS RESEARCH
Volume 228, Issue -, Pages 114-123Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.virusres.2016.11.029
Keywords
VCP; WNV replication; Early steps; Genome replication
Categories
Funding
- Program for Leading Graduate Schools Fostering Global Leaders in Veterinary Science for Contributing to One Health
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [16H06429, 16K21723, 16H06431]
- Grants-in-Aid for Scientific Research [16H06431, 15K19069] Funding Source: KAKEN
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Valosin-containing protein (VCP) is classified as a member of the type II AAA(+) ATPase protein family. VCP functions in several cellular processes, including protein degradation, membrane fusion, vesicular trafficking and disassembly of stress granules. Moreover, VCP is considered to play a role in the replication of several viruses, albeit through different mechanisms. In the present study, we have investigated the role of VCP in West Nile virus (WNV) infection. Endogenous VCP expression was inhibited using either VCP inhibitors or by siRNA knockdown. It could be shown that the inhibition of endogenous VCP expression significantly inhibited WNV infection. The entry assay revealed that silencing of endogenous VCP caused a significant reduction in the expression levels of WNV-RNA compared to control siRNA-treated cells. This indicates that VCP may play a role in early steps either the binding or entry steps of the WNV life cycle. Using WNV virus like particles and WNV-DNA-based replicon, it could be demonstrated that perturbation of VCP expression decreased levels of newly synthesized WNV genomic RNA. These findings suggest that VCP is involved in early steps and during genome replication of the WNV life cycle. (C) 2016 Elsevier B.V. All rights reserved.
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