Hepatitis C Virus NS5A Protein Interacts with Phosphatidylinositol 4-Kinase Type IIIα and Regulates Viral Propagation
Hepatitis C Virus NS5A Protein Interacts with Phosphatidylinositol 4-Kinase Type IIIα and Regulates Viral Propagation
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DOI：
10.1074/jbc.m110.194472
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发表时间：
2011-04-01
影响因子：
4.8
通讯作者：
Hwang, Soon B.
中科院分区：
文献类型：
--
作者：
Lim, Yun-Sook;Hwang, Soon B.
Hepatitis C Virus (HCV) nonstructural 5A (NS5A) is a pleiotropic protein involved in viralRNAreplication and modulation of the cellular physiology in HCV-infected cells. Toelucidate the mechanisms of the HCV life cycle, we identified cellular factors interacting with the NS5A protein in HCV-infected cells. Huh7.5 cells were electroporated with HCV Jc1 RNA. Cellular factors associated with HCV NS5A were identified by immunoprecipitation with Dynabead-conjugated NS5A antibody and LC-MS/MS. Phosphatidylinositol 4-kinase type III alpha (PI4KIII alpha) was identified as a binding partner for the NS5A protein. NS5A derived from both genotypes 1b and 2a interacted with PI4KIII alpha. NS5A interacted with PI4KIII alpha through amino acids 401-600 of PI4KIII alpha and domain I of NS5A. Interference of the protein interaction between NS5A and PI4KIII alpha decreased HCV propagation. Knockdown of PI4KIII alpha significantly reduced HCV replication in Huh7 cells harboring the subgenomic replicon and in Huh7.5 cells infected with cell culture grown virus (HCVcc). Silencing of PI4KIII alpha further inhibited HCV release into the tissue culture medium. NS5A may recruit PI4KIII alpha to the HCV RNA replication complex. These data suggest that PI4KIII alpha is an essential host factor that supports HCV proliferation and therefore PI4KIII alpha may be a legitimate target for anti-HCV therapy.
