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 language | English |
|---|---|
| Article number | e7498 |
| Journal | PLoS One |
| Volume | 4 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 16 2009 |
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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 journal › Article
}
TY - JOUR
T1 - Up-regulation of hepatitis C virus replication and production by inhibition of MEK/ERK signaling
AU - Ndjomou, Jean
AU - Park, In Woo
AU - Liu, Ying
AU - Mayo, Lindsey
AU - He, Johnny J.
PY - 2009/10/16
Y1 - 2009/10/16
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=70449379570&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0007498
DO - 10.1371/journal.pone.0007498
M3 - Article
C2 - 19834602
AN - SCOPUS:70449379570
VL - 4
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e7498
ER -