Asmal, MohammedSeaman, MichaelLin, WenyuChung, RaymondLetvin, Norman LGeiben-Lynn, Ralf2013-04-232012Asmal, Mohammed, Michael S. Seaman, Wenyu Lin, Raymond Taeyong Chung, Norman L. Letvin, and Ralf Geiben-Lynn. 2012. Inhibition of HCV by the serpin antithrombin III. Virology Journal 9(1): 226.1743-422Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10579666Background: Although 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. Results: We 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. Conclusions: Our findings suggest that ATIII stimulates a novel innate antiviral host cell defense different from current treatment options.en-USAntithrombin IIIHepatitis C virusOR6 replicon cellsNFκBP38 MAPKERK1/2Journal Article2013-04-2310.1186/1743-422X-9-226