Hepatitis C virus infection causes apoptosis and pyroptosis in both infected and bystander cells

Kofahi, Hassan (2017) Hepatitis C virus infection causes apoptosis and pyroptosis in both infected and bystander cells. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Hepatitis C virus (HCV) infection is a global health challenge affecting 3% of the world’s population. Chronically infected individuals are at high risk of developing progressive liver diseases including cirrhosis and hepatocellular carcinoma (HCC). Apoptosis and pyroptosis are two forms of programmed cell death (PCD) that can cause different pathological outcomes. Studying the induction of these forms of PCD by HCV will help in understanding the development of liver complications and might be useful in designing new treatment. We used a tissue culture adapted strain of HCV (JFH1 ) to study the effect ofᵀ infection on the induction of these two forms of PCD in infected and bystander cells. We found that HCV infection reduces the proliferation rate and induces PCD in the infected cell population. Further analysis revealed that two forms of PCD are induced: apoptosis and pyroptosis, as we were able to detect the activation of both caspase-3 and caspase-1 and we confirmed their role in the induction of PCD. NLRP3 inflammasome activation was found to play a role in the induction of pyroptosis. By performing a co-culture assay containing Huh-7.5 cells and HCV-non-permissive cell lines, we were able to detect the induction of both bystander apoptosis and bystander pyroptosis in the non-permissive cells. Bystander apoptosis, but not bystander pyroptosis, was found to require cell-cell contact between the infected and the bystander cell. In summary, we demonstrated that HCV infection can cause apoptosis and pyroptosis, and both of these forms of PCD can be induced in uninfected bystander cells.

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