Hepatitis C Virus Infection of Cultured Human Hepatoma Cells Causes Apoptosis and Pyroptosis in Both Infected and Bystander Cells

Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one opera...

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Bibliographic Details
Published in:	Scientific reports Vol. 6; no. 1; p. 37433
Main Authors:	Kofahi, H. M., Taylor, N. G. A., Hirasawa, K., Grant, M. D., Russell, R. S.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 15-12-2016 Nature Publishing Group
Subjects:	13 13/106 13/109 13/2 13/31 692/420/254 692/420/2780/262/2106/2517 Apoptosis Apoptosis - genetics Bystander Effect Caspase Caspase 1 - genetics Caspase 1 - metabolism Caspase 3 - genetics Caspase 3 - metabolism Caspase-1 Caspase-3 Cell adhesion Cell culture Cell death Cell Line, Tumor Cell Proliferation Cirrhosis Coculture Techniques Gene Expression Regulation Hepacivirus - growth & development Hepacivirus - pathogenicity Hepatitis Hepatitis C Hepatocellular carcinoma Hepatocytes - metabolism Hepatocytes - virology Hepatoma Host-Pathogen Interactions Humanities and Social Sciences Humans Infections Inflammasomes Inflammasomes - metabolism Liver cancer Liver cirrhosis Liver diseases multidisciplinary NLR Family, Pyrin Domain-Containing 3 Protein - genetics NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Pyroptosis Pyroptosis - genetics Science Signal Transduction Tissue culture
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Summary:	Individuals infected with hepatitis C virus (HCV) are at high risk of developing progressive liver disease, including cirrhosis and hepatocellular carcinoma (HCC). How HCV infection causes liver destruction has been of significant interest for many years, and apoptosis has been proposed as one operative mechanism. In this study, we employed a tissue culture-adapted strain of HCV (JFH1 T ) to test effects of HCV infection on induction of programmed cell death (PCD) in Huh-7.5 cells. We found that HCV infection reduced the proliferation rate and induced caspase-3-mediated apoptosis in the infected cell population. However, in addition to apoptosis, we also observed infected cells undergoing caspase-1-mediated pyroptosis, which was induced by NLRP3 inflammasome activation. By co-culturing HCV-infected Huh-7.5 cells with an HCV-non-permissive cell line, we also demonstrated induction of both apoptosis and pyroptosis in uninfected cells. Bystander apoptosis, but not bystander pyroptosis, required cell-cell contact between infected and bystander cells. In summary, these findings provide new information on mechanisms of cell death in response to HCV infection. The observation that both apoptosis and pyroptosis can be induced in bystander cells extends our understanding of HCV-induced pathogenesis in the liver.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep37433