Inhibition of HCV by the serpin antithrombin IIIReport as inadecuate

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Virology Journal

, 9:226

First Online: 02 October 2012Received: 28 February 2012Accepted: 27 September 2012


BackgroundAlthough there have been dramatic strides made recently in the treatment of chronic hepatitis C virus infection, interferon-α based therapy remains challenging for certain populations, including those with unfavorable IL28B genotypes, psychiatric co-morbidity, HIV co-infection, and decompensated liver disease. We have recently shown that ATIII, a serine protease inhibitor serpin, has broad antiviral properties.

ResultsWe now show that ATIII is capable of inhibiting HCV in the OR6 replicon model at micromolar concentrations. At a mechanistic level using gene-expression arrays, we found that ATIII treatment down-regulated multiple host cell signal transduction factors involved in the pathogenesis of cirrhosis and hepatocellular carcinoma, including Jun, Myc and BMP2. Using a protein interactive network analysis we found that changes in gene-expression caused by ATIII were dependent on three nodes previously implicated in HCV disease progression or HCV replication: NFκB, P38 MAPK, and ERK1-2.

ConclusionsOur findings suggest that ATIII stimulates a novel innate antiviral host cell defense different from current treatment options.

KeywordsAntithrombin III Hepatitis C virus OR6 replicon cells NFκB P38 MAPK ERK1-2 Electronic supplementary materialThe online version of this article doi:10.1186-1743-422X-9-226 contains supplementary material, which is available to authorized users.

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Author: Mohammed Asmal - Michael Seaman - Wenyu Lin - Raymond T Chung - Norman L Letvin - Ralf Geiben-Lynn


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