title: Valosin-containing protein (VCP/p97) plays a role in the replication of West Nile virus.
abstract: 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.
authors.affiliation: Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan.
authors.forename: Wallaya
authors.initials: W
authors.lastname: Phongphaew
authors.affiliation: Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan; Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo 001-0020, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan.
authors.forename: Michihito
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Global Institution for Collaborative Researches and Education (GI-CoRE), Global Station for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan; National Virus Reference Laboratory, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Carr
authors.affiliation: Global Institution for Collaborative Researches and Education (GI-CoRE), Global Station for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan; Center for Research in Infectious Diseases, University College of Dublin, Belfield, Dublin 4, Dublin, Ireland; Global Virus Network (GVN), The Institute of Human Virology, University of Maryland, 22S. Greene Street, Baltimore, MD 21201, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Hall
authors.affiliation: Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Orba
authors.affiliation: Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan; Global Institution for Collaborative Researches and Education (GI-CoRE), Global Station for Zoonosis Control, Hokkaido University, N20, W10, Kita-ku, Sapporo 001-0020, Japan; Global Virus Network (GVN), The Institute of Human Virology, University of Maryland, 22S. Greene Street, Baltimore, MD 21201, USA. Electronic address: h-sawa@czc.hokudai.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
mesh_terms: D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D016679:Genome, Viral; D006801:Humans; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics; D000074405:Valosin Containing Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D014901:West Nile Fever / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D014902:West Nile virus / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D012367:RNA, Viral; D000074405:Valosin Containing Protein
keywords: Early steps; Genome replication; VCP; WNV replication