Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence

Mankouri, J., Dallas, M. L. ORCID: https://orcid.org/0000-0002-5190-0522, Hughes, M. E., Griffin, S. D. C., Macdonald, A., Peers, C. and Harris, M. (2009) Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence. Proceedings of the National Academy of Sciences of the United States of America, 106 (37). pp. 15903-15908. ISSN 0027-8424 doi: 10.1073/pnas.0906798106

Abstract/Summary

An estimated 3% of the global population are infected with hepatitis C virus (HCV), and the majority of these individuals will develop chronic liver disease. As with other chronic viruses, establishment of persistent infection requires that HCV-infected cells must be refractory to a range of pro-apoptotic stimuli. In response to oxidative stress, amplification of an outward K(+) current mediated by the Kv2.1 channel, precedes the onset of apoptosis. We show here that in human hepatoma cells either infected with HCV or harboring an HCV subgenomic replicon, oxidative stress failed to initiate apoptosis via Kv2.1. The HCV NS5A protein mediated this effect by inhibiting oxidative stress-induced p38 MAPK phosphorylation of Kv2.1. The inhibition of a host cell K(+) channel by a viral protein is a hitherto undescribed viral anti-apoptotic mechanism and represents a potential target for antiviral therapy.