PMID- 20069613 OWN - NLM STAT- MEDLINE DCOM- 20100519 LR - 20100304 IS - 1099-1654 (Electronic) IS - 1052-9276 (Linking) VI - 20 IP - 2 DP - 2010 Mar TI - Hepatitis C virus nonstructural protein 4B: a journey into unexplored territory. PG - 117-29 LID - 10.1002/rmv.640 [doi] AB - 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. CI - (c) 2010 John Wiley & Sons, Ltd. FAU - Gouttenoire, Jerome AU - Gouttenoire J AD - Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland. FAU - Penin, Francois AU - Penin F FAU - Moradpour, Darius AU - Moradpour D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Rev Med Virol JT - Reviews in medical virology JID - 9112448 RN - 0 (Membrane Proteins) RN - 0 (NS4B protein, flavivirus) RN - 0 (RNA, Viral) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - Hepacivirus/*physiology MH - Membrane Proteins/chemistry/physiology MH - Models, Biological MH - Protein Binding MH - Protein Processing, Post-Translational MH - Protein Structure, Tertiary MH - RNA, Viral/metabolism MH - Viral Nonstructural Proteins/chemistry/*physiology MH - *Virus Assembly MH - *Virus Replication RF - 120 EDAT- 2010/01/14 06:00 MHDA- 2010/05/21 06:00 CRDT- 2010/01/14 06:00 PHST- 2010/01/14 06:00 [entrez] PHST- 2010/01/14 06:00 [pubmed] PHST- 2010/05/21 06:00 [medline] AID - 10.1002/rmv.640 [doi] PST - ppublish SO - Rev Med Virol. 2010 Mar;20(2):117-29. doi: 10.1002/rmv.640.