Open AccessAssociation of Hepatitis C Virus Replication Complexes with Microtubules and Actin Filaments Is Dependent on the Interaction of NS3 and NS5A
Author(s) -
Chao-Kuen Lai,
KingSong Jeng,
Keigo Machida,
Michael M. C. Lai
Publication year - 2008
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00398-08
Subject(s) - ns5a , microtubule , biology , ns3 , microbiology and biotechnology , cytochalasin d , actin , tubulin , cytoskeleton , viral replication , virology , virus , hepatitis c virus , cell , biochemistry , hepacivirus
The hepatitis C virus (HCV) RNA replication complex (RC), which is composed of viral nonstructural (NS) proteins and host cellular proteins, replicates the viral RNA genome in association with intracellular membranes. Two viral NS proteins, NS3 and NS5A, are essential elements of the RC. Here, by using immunoprecipitation and fluorescence resonance energy transfer assays, we demonstrated that NS3 and NS5A interact with tubulin and actin. Furthermore, immunofluorescence microscopy and electron microscopy revealed that HCV RCs were aligned along microtubules and actin filaments in both HCV replicon cells and HCV-infected cells. In addition, the movement of RCs was inhibited when microtubules or actin filaments were depolymerized by colchicine and cytochalasin B, respectively. Based on our observations, we propose that microtubules and actin filaments provide the tracks for the movement of HCV RCs to other regions in the cell, and the molecular interactions between RCs and microtubules, or RCs and actin filaments, are mediated by NS3 and NS5A.