Ndjomou, JeanPark, In-wooLiu, YingMayo, Lindsey D.He, Johnny J.2020-04-012020-04-012009Ndjomou, J., Park, I. W., Liu, Y., Mayo, L. D., & He, J. J. (2009). Up-regulation of hepatitis C virus replication and production by inhibition of MEK/ERK signaling. PloS one, 4(10), e7498. https://doi.org/10.1371/journal.pone.0007498https://hdl.handle.net/1805/22451Background 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.en-USAttribution 4.0 InternationalMEK/ERK signaling pathwayRNA virusesHepatitis C virus (HCV)Article