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Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C Virus Entry.

Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C Virus Entry.

Authors :
Chorong Park
Saehong Min
Eun-Mee Park
Yun-Sook Lim
Sangmin Kang
Tetsuro Suzuki
Eui-Cheol Shin
Hwang, Soon B.
Source :
Journal of Virology. Oct2015, Vol. 89 Issue 20, p10073-10086. 14p.
Publication Year :
2015

Abstract

The life cycle of hepatitis C virus (HCV) is highly dependent on host cellular proteins for virus propagation. In order to identify the cellular factors involved in HCV propagation, we performed protein microarray assay using the HCV nonstructural 5A (NS5A) protein as a probe. Of ~9,000 human cellular proteins immobilized in a microarray, approximately 90 cellular proteins were identified as NS5A interactors. Of these candidates, Pim1, a member of serine/threonine kinase family composed of three different isoforms (Pim1, Pim2, and Pim3), was selected for further study. Pim kinases share a consensus sequence which overlaps with kinase activity. Pim kinase activity has been implicated in tumorigenesis. In the present study, we verified the physical interaction between NS5A and Pim1 by both in vitro pulldown and coimmunoprecipitation assays. Pim1 interacted with NS5A through amino acid residues 141 to 180 of Pim1. We demonstrated that protein stability of Pim1 was increased by NS5A protein and this increase was mediated by protein interplay. Small interfering RNA (siRNA)-mediated knockdown or pharmacological inhibition of Pim kinase abrogated HCV propagation. By employing HCV pseudoparticle entry and single-cycle HCV infection assays, we further demonstrated that Pim kinase was involved in HCV entry at a postbinding step. These data suggest that Pim kinase may represent a new host factor for HCV entry. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022538X
Volume :
89
Issue :
20
Database :
Academic Search Index
Journal :
Journal of Virology
Publication Type :
Academic Journal
Accession number :
120255594
Full Text :
https://doi.org/10.1128/JVI.01707-15