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Journal of Virology, October 2004, p. 11288-11295, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11288-11295.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Nucleotide Binding Motif in Hepatitis C Virus (HCV) NS4B Mediates HCV RNA Replication

Shirit Einav,1,{dagger} Menashe Elazar,1,{dagger} Tsafi Danieli,2 and Jeffrey S. Glenn1,3*

Division of Gastroenterology and Hepatology, Stanford University School of Medicine,1 Veterans Administration Medical Center, Palo Alto, California,3 Protein Expression Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel2

Received 1 March 2004/ Accepted 6 June 2004

Hepatitis C virus (HCV) is a major cause of viral hepatitis. There is no effective therapy for most patients. We have identified a nucleotide binding motif (NBM) in one of the virus's nonstructural proteins, NS4B. This structural motif binds and hydrolyzes GTP and is conserved across HCV isolates. Genetically disrupting the NBM impairs GTP binding and hydrolysis and dramatically inhibits HCV RNA replication. These results have exciting implications for the HCV life cycle and novel antiviral strategies.

* Corresponding author. Mailing address: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR Building, Room 3115, 269 Campus Dr., Palo Alto, CA 94305-5187. Phone: (650) 725-3373. Fax: (650) 723-3032. E-mail: jeffrey.glenn{at}stanford.edu.

{dagger} S.E. and M.E. contributed equally to this work.

Journal of Virology, October 2004, p. 11288-11295, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11288-11295.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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