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      Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory.

      1 , ,
      Reviews in medical virology
      Wiley

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          Abstract

          Hepatitis C virus (HCV) is a positive-strand RNA virus that replicates its genome in a membrane-associated replication complex. Nonstructural protein 4B (NS4B) induces the specific membrane alteration, designated as membranous web (MW), that harbours this complex. HCV NS4B is an integral membrane protein predicted to comprise four transmembrane segments in its central part. The N-terminal part comprises two amphipathic alpha-helices of which the second has the potential to traverse the membrane bilayer, likely upon oligomerisation. The C-terminal part comprises a predicted highly conserved alpha-helix, a membrane-associated amphipathic alpha-helix and two reported palmitoylation sites. NS4B interacts with other viral nonstructural proteins and has been reported to bind viral RNA. In addition, it was found to harbour an NTPase activity. Finally, NS4B has recently been found to have a role in viral assembly. Much work needs to be done with respect to further dissecting these multiple functions as well as providing a refined membrane topology and complete structure of NS4B. Progress in this direction should yield important insights into the functional architecture of the HCV replication complex and may reveal new opportunities for antiviral intervention against a leading cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide.

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          Author and article information

          Journal
          Rev Med Virol
          Reviews in medical virology
          Wiley
          1099-1654
          1052-9276
          Mar 2010
          : 20
          : 2
          Affiliations
          [1 ] Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
          Article
          10.1002/rmv.640
          20069613
          42eb1178-4185-43c5-b170-2c471a3e9fb9
          (c) 2010 John Wiley & Sons, Ltd.
          History

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