Up-regulation of hepatitis C virus replication and production by inhibition of MEK/ERK signaling

Jean Ndjomou, In Woo Park, Ying Liu, Lindsey Mayo, Johnny J. He

Research output: Contribution to journalArticle

14 Citations (Scopus)

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-α (IFN-α) 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.

Original languageEnglish
Article numbere7498
JournalPLoS One
Volume4
Issue number10
DOIs
StatePublished - Oct 16 2009

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Hepatitis C virus
Mitogen-Activated Protein Kinase Kinases
Virus Replication
virus replication
Viruses
Hepacivirus
Up-Regulation
MAP Kinase Signaling System
RNA Viruses
RNA
Gene expression
Gene Expression
gene expression
viruses
interferons
Interferons
translation (genetics)
hepatocytes
Antiviral Agents
Liver

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Up-regulation of hepatitis C virus replication and production by inhibition of MEK/ERK signaling. / Ndjomou, Jean; Park, In Woo; Liu, Ying; Mayo, Lindsey; He, Johnny J.

In: PLoS One, Vol. 4, No. 10, e7498, 16.10.2009.

Research output: Contribution to journalArticle

Ndjomou, Jean ; Park, In Woo ; Liu, Ying ; Mayo, Lindsey ; He, Johnny J. / Up-regulation of hepatitis C virus replication and production by inhibition of MEK/ERK signaling. In: PLoS One. 2009 ; Vol. 4, No. 10.
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