RRC ID 45220
Author Kobayashi S, Orba Y, Yamaguchi H, Takahashi K, Sasaki M, Hasebe R, Kimura T, Sawa H.
Title Autophagy inhibits viral genome replication and gene expression stages in West Nile virus infection.
Journal Virus Res
Abstract Autophagy is a lysosomal degradation pathway that is implicated in many viral infections. However, its role in West Nile virus (WNV) infection remains controversial. In the present study, we examined the relationship between WNV infection and autophagy in infected cells. We demonstrated that LC3-II expression, a molecular marker for autophagosomal membranes, was enhanced in WNV-infected cells 6h post-infection. LC3-II expression was further enhanced in WNV-inoculated cells when treated with a lysosomal protease inhibitor. Meanwhile, WNV replication in cells lacking Atg5, an essential factor for autophagy, was increased compared with replication in wild-type cells. In addition, WNV replication was inhibited in cells lacking Atg5 when they were transfected with an ATG5 expression plasmid. These results suggest an antiviral role for autophagy in WNV-infected cells. We also examined which viral replication stages were affected by autophagy by using a Tat-beclin 1 peptide to induce autophagy and pseudo-infectious WNV reporter virus particles (WNV-RVPs) that monitor viral genome replication and gene expression stages via GFP expression. We found that autophagy induction in HeLa cells by Tat-beclin 1 peptide 3h after WNV inoculation inhibited viral replication, and GFP expression was significantly inhibited in wild-type cells when compared with cells lacking Atg5. Taken together, these results suggest that autophagy is induced by WNV infection, and that this induction inhibits WNV replication at the viral genome replication and gene expression stages.
Volume 191
Pages 83-91
Published 2014-10-13
DOI 10.1016/j.virusres.2014.07.016
PII S0168-1702(14)00282-2
PMID 25091564
MeSH Autophagy* Autophagy-Related Protein 5 Down-Regulation Gene Expression Regulation, Viral* Genome, Viral* Humans Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Viral Proteins / genetics* Viral Proteins / metabolism Virus Replication* West Nile Fever / genetics West Nile Fever / metabolism West Nile Fever / physiopathology* West Nile Fever / virology West Nile virus / genetics West Nile virus / physiology*
IF 2.934
Times Cited 22
Human and Animal Cells Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711)