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Proteomic Analysis of the HCV Encoded Peptide NS5 A Cellular Protein Complex
Author(s) -
French Samuel Wheeler,
Gonzalez Oscar,
Raychaudhuri Santanu,
Fontanes Vanessa,
Loo Rachel,
Loo Joseph,
Dasgupta Asim
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.898.13
Subject(s) - ns5a , hepatocellular carcinoma , hepatitis c virus , biology , viral replication , cancer research , cell , virology , hepacivirus , virus , biochemistry
Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. One of most common causes of HCC includes infection with hepatitis C virus (HCV) in association with cirrhosis. The HCV protein NS5A is required for viral replication and has been implicated in the development of HCC through alteration of cell signaling. The oncogenic potential of NS5A and its impact on cell signaling renders it a reasonable target for therapeutic intervention. Aim: To develop a system to determine cellular signaling pathways altered by the HCV protein NS5A through identification of proteins it form complexes with in cellular extracts. Methods: NS5A protein complexes were purified from stable cell lines expressing NS5AFlag fusion protein, resolved by SDS‐PAGE and silver stained. Results: Complex purification was optimized and at least two proteins (approximately 40 and 70 kDa) were identified as potential NS5A associated proteins. Conclusions: We have identified 40 kDa and 70 kDa cellular protein members of the NS5A complex that may play a role in viral replication or augment the NS5A antiviral response mediated through PKR. Pharmacologic inhibition of these interactions may reduce viral replication and ultimately prevent hepatocellular carcinoma. Supported by: Stein/Oppenheimer Endowment Award, CURE Pilot and Feasibility Study, CURE Named New Investigator Award