Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Cell Line, Tumor
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GTP Phosphohydrolases / metabolism
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Gene Expression Regulation, Viral*
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Guanosine Triphosphate / metabolism*
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Hepacivirus / genetics*
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Hepacivirus / metabolism
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Humans
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Hydrolysis
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Molecular Sequence Data
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RNA, Viral / biosynthesis*
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Viral Nonstructural Proteins / chemistry*
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / metabolism
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Virus Replication
Substances
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NS4 protein, hepatitis C virus
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RNA, Viral
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Viral Nonstructural Proteins
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Guanosine Triphosphate
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GTP Phosphohydrolases