Requirement of Cellular DDX3 for Hepatitis C Virus Replication is Unrelated to Its Interaction with the Viral Core Protein

Overview

Journal J Gen Virol

Specialty Microbiology

Date 2009 Oct 2

PMID 19793905

Citations 58

Authors

Allan G N Angus

David Dalrymple

Steeve Boulant

David R McGivern

Reginald F Clayton

Martin J Scott

Richard Adair

Susan Graham

Ania M Owsianka

Paul Targett-Adams

Kui Li

Takaji Wakita

John McLauchlan

Stanley M Lemon

Arvind H Patel

Affiliations

Soon will be listed here.

Abstract

The cellular DEAD-box protein DDX3 was recently shown to be essential for hepatitis C virus (HCV) replication. Prior to that, we had reported that HCV core binds to DDX3 in yeast-two hybrid and transient transfection assays. Here, we confirm by co-immunoprecipitation that this interaction occurs in cells replicating the JFH1 virus. Consistent with this result, immunofluorescence staining of infected cells revealed a dramatic redistribution of cytoplasmic DDX3 by core protein to the virus assembly sites around lipid droplets. Given this close association of DDX3 with core and lipid droplets, and its involvement in virus replication, we investigated the importance of this host factor in the virus life cycle. Mutagenesis studies located a single amino acid in the N-terminal domain of JFH1 core that when changed to alanine significantly abrogated this interaction. Surprisingly, this mutation did not alter infectious virus production and RNA replication, indicating that the core-DDX3 interaction is dispensable in the HCV life cycle. Consistent with previous studies, siRNA-led knockdown of DDX3 lowered virus production and RNA replication levels of both WT JFH1 and the mutant virus unable to bind DDX3. Thus, our study shows for the first time that the requirement of DDX3 for HCV replication is unrelated to its interaction with the viral core protein.

Citing Articles

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