The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection.

The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection. Research Abstract Details 

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The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection. Abstract Text:

Hepatitis C virus (HCV) is an important cause of chronic liver disease and is complicated by hepatocellular carcinoma (HCC). Mechanisms whereby the virus promotes cellular transformation are poorly understood. We hypothesized that the guanosine triphosphatase activity encoded in the HCV NS4B protein's nucleotide binding motif (NBM) might play a role in the transformation process. Here we report that NS4B can transform NIH-3T3 cells, leading to tumor formation in vivo. This transformation was independent of co-transfection with activated Ha-ras. Detailed analyses of NS4B mutants revealed that this transforming activity could be progressively inhibited and completely abrogated by increasing genetic impairment of the NS4B nucleotide binding motif. Conclusion: NS4B has in vitro and in vivo tumorigenic potential, and the NS4B transforming activity is indeed mediated by its NBM. Moreover, our results suggest that pharmacological inhibition of the latter might inhibit not only HCV replication but also the associated HCC. (HEPATOLOGY 2008.).

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The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hepatology (Baltimore, Md.)

VOLUME: 47

Page Numbers: 827-35

Journal Abbreviation: Hepatology

ISSN: 1527-3350

DAY: 4

MONTH: Mar

YEAR: 2008

The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection. Information

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LANGUAGE: eng

NlmUniqueID: 8302946

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Grant and Affiliation Information for The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection.

AFFILIATION: Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California.

Country: United States

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MEDLINETA: Hepatology

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