Autophagy protein ATG5 interacts transiently with the hepatitis polymerase (NS5B) early during infection

被引:131
作者
Guevin, Carl [1 ]
Manna, David [2 ]
Belanger, Claudia [1 ]
Konan, Kouacou V. [2 ]
Mak, Paul [3 ]
Labonte, Patrick [1 ]
机构
[1] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ H7V 1B7, Canada
[2] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA
[3] Wyeth Res, Infect Dis, Pearl River, NY USA
基金
加拿大自然科学与工程研究理事会;
关键词
HCV; Autophagy; ATG5; RdRp; NS5B; siRNA; VIRAL REPLICATION COMPLEX; DEPENDENT RNA-POLYMERASE; DOUBLE-MEMBRANE VESICLES; C VIRUS-REPLICATION; NONSTRUCTURAL PROTEINS; ENDOPLASMIC-RETICULUM; POLIOVIRUS INFECTION; IN-VITRO; CELLS; CYTOPLASM;
D O I
10.1016/j.virol.2010.05.032
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Autophagy is an important cellular process by which ATG5 initiates the formation of double membrane vesicles (DMVs). Upon infection, DMVs have been shown to harbor the replicase complex of positive-strand RNA viruses such as MHV, poliovirus. and equine arteritis virus. Recently, it has been shown that autophagy proteins are proviral factors that favor initiation of hepatitis C virus (HCV) infection Here, we identified ATG5 as an interacting protein for the HCV NS5B ATG5/NS5B interaction was confirmed by co-IP and metabolic labeling studies. Furthermore. ATG5 protein colocalizes with NS4B, a constituent of the membranous web Importantly, immunofluorescence staining demonstrated a strong colocalization of ATG5 and NS5B within perinuclear regions of infected cells at 2 days postinfection However, colocalization was completely lacking at 5 DPI, suggesting that HCV utilizes ATG5 as a proviral factor during the onset of viral infection Finally, inhibition of autophagy through ATG5 silencing blocks HCV replication. (C) 2010 Elsevier Inc All rights reserved
引用
收藏
页码:1 / 7
页数:7
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