Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening.

Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. Research Abstract Details 

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Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. Abstract Text:

Lubica Supekova,Frantisek Supek,Jongkook Lee,Shawn Chen,Nathanael Gray,John P Pezacki,Achim Schlapbach,Peter G Schultz,Lubica Supekova,Frantisek Supek,Jongkook Lee,Shawn Chen,Nathanael Gray,John P Pezacki,Achim Schlapbach,Peter G Schultz,

The propagation of the hepatitis C virus (HCV) is a complex process that requires both host and viral proteins. To facilitate identification of host cell factors that are required for HCV replication, we screened a panel of small interference RNAs that preferentially target human protein kinases using an HCV replicon expressing the firefly luciferase gene as a genetic reporter. Small interference RNAs specific for three human kinases, Csk, Jak1, and Vrk1, were identified that reproducibly reduce viral RNA and viral protein levels in HCV replicon-bearing cells. Treatment of replicon cells with a small molecule inhibitor of Csk also resulted in a significant reduction in HCV RNA and proteins, further supporting a role for Csk in HCV replication. The effects of siRNAs targeting eight kinases known to be negatively regulated by Csk were then examined; knock down of one of these kinases, Fyn, resulted in up-regulation of the HCV replicon, suggesting that Csk mediates its effect on HCV replication through Fyn. This conclusion was further corroborated by demonstration that replicon cells treated with Csk inhibitor contained lower levels of the phosphorylated form of Fyn than control cells.

Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. Publishing Authors By Initials

L Supekova,F Supek,J Lee,S Chen,N Gray,JP Pezacki,A Schlapbach,PG Schultz,L Supekova,F Supek,J Lee,S Chen,N Gray,JP Pezacki,A Schlapbach,PG Schultz,

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Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The Journal of biological chemistry

VOLUME: 283

Page Numbers: 29-36

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 19

MONTH: 10

YEAR: 2007

Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

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AFFILIATION: Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037.

Country: United States

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MEDLINETA: J Biol Chem

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