Positive effect of the hepatitis C virus nonstructural 5A protein on viral multiplication

Archives of Virology
D BonteG Duverlie

Abstract

Hepatitis C virus infection (HCV), is a major cause of liver disease worldwide, and are frequently resistant to the interferon alpha treatment. The nonstructural (NS) 5A protein of HCV has been proposed to be involved in this resistance. Additional studies have pointed out a role for NS5A in several other cellular interactions as well as an important role of its adaptative mutations in HCV genome replication. However, no infectious system is available to assess the role of NS5A in the HCV life cycle. Thus, we have constructed a recombinant system directly demonstrating for the first time that the expression of NS5A confers a multiplicative advantage to Sindbis virus, a virus close to HCV. This advantage seemed to be related to an anti-apoptotic effect of the NS5A protein. At a later stage, a possible nuclear localization of NS5A was observed, likely due to apoptotic cleavages of this protein. The NS5A protein was also shown to induce the interleukin-8 (IL-8) mRNA and to activate the NF-kappaB pathway independently of the Sindbis virus. Together, our data suggest that the activation of NF-kappaB could lead to the anti-apoptotic activity of NS5A and explain the viral multiplicative advantage conferred by the expression of the NS5...Continue Reading

Citations

Mar 17, 2010·Oncogene·W-L Tsai, R T Chung
Jul 29, 2006·Journal of Virology·Bon Chang A KooStephen J Polyak
Oct 10, 2008·Journal of Virology·Mathis Heydtmann
Dec 3, 2009·Virology Journal·Christoph P BergGerburg M Stein
Nov 10, 2013·Journal of Gastrointestinal Cancer·Michael C Kew
Sep 27, 2007·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Aldona Kasprzak, Agnieszka Adamek
Aug 13, 2013·PloS One·Olga AbianAdrian Velazquez-Campoy
Dec 25, 2010·Therapeutic Advances in Gastroenterology·Jacqueline G O'Leary, Gary L Davis
Jan 1, 2013·Biology·Tatsuo KandaMasao Omata
Oct 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yi YuJianguo Wu

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