Up-regulation of Hepatitis C Virus Replication and Production by Inhibition of MEK/ERK Signaling

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Oct 17

PMID 19834602

Citations 12

Authors

Jean Ndjomou

In-Woo Park

Ying Liu

Lindsey D Mayo

Johnny J He

Affiliations

Soon will be listed here.

Abstract

Background: Viruses interact with and exploit the host cellular machinery for their multiplication and propagation. The MEK/ERK signaling pathway positively regulates replication of many RNA viruses. However, whether and how this signaling pathway affects hepatitis C virus (HCV) replication and production is not well understood.

Methods And Results: In this study, we took advantage of two well-characterized MEK/ERK inhibitors and MEK/ERK dominant negative mutants and investigated the roles of the MEK/ERK signaling pathway in HCV gene expression and replication. We showed that inhibition of MEK/ERK signaling enhanced HCV gene expression, plus- and minus-strand RNA synthesis, and virus production. In addition, we showed that this enhancement was independent of interferon-alpha (IFN-alpha) antiviral activity and did not require prior activation of the MEK/ERK signaling pathway. Furthermore, we showed that only MEK and ERK-2 but not ERK-1 was involved in HCV replication, likely through regulation of HCV RNA translation.

Conclusions: Taken together, these results demonstrate a negative regulatory role of the MEK/ERK signaling pathway in HCV replication and suggest a potential risk in targeting this signaling pathway to treat and prevent neoplastic transformation of HCV-infected liver cells.

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