HCV-Mediated Apoptosis of Hepatocytes in Culture and Viral Pathogenesis

• Published in: PloS one Vol. 11; no. 6; p. e0155708
• Main Authors: Silberstein, Erica, Ulitzky, Laura, Lima, Livia Alves, Cehan, Nicoleta, Teixeira-Carvalho, Andréa, Roingeard, Philippe, Taylor, Deborah R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.06.2016; Public Library of Science (PLoS)
• Subjects: Analysis; Antiviral agents; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Autophagy; Biology and Life Sciences; Biopsy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Care and treatment; Caspase; Cell culture; Cell death; Chronic illnesses; Chronic infection; Cirrhosis; Complications and side effects; Cytokines; Electron microscopy; Fibrosis; Gene expression; Genotype & phenotype; Genotypes; Health aspects; Hepacivirus - pathogenicity; Hepatitis; Hepatitis C; Hepatitis C - metabolism; Hepatitis C - pathology; Hepatitis C - virology; Hepatitis C virus; Hepatocytes; Hepatocytes - metabolism; Hepatocytes - pathology; Hepatocytes - virology; Hepatology; Hepatoma; Humans; Infections; Inflammation; Kinases; Laboratories; Liver; Liver cancer; Liver cirrhosis; Liver diseases; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - virology; Markers; Medicine and health sciences; Metabolism; p53 Protein; Pathogenesis; Proteins; Research and Analysis Methods; Rodents; Studies; Tumor Cells, Cultured; Tumor necrosis factor-TNF; Tumor suppressor genes; Viruses; California; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0155708

Chronic Hepatitis C Virus (HCV) infection is associated with progressive liver injury and subsequent development of fibrosis and cirrhosis. The death of hepatocytes results in the release of cytokines that induce inflammatory and fibrotic responses. The mechanism of liver damage is still under investigation but both apoptosis and immune-mediated processes may play roles. By observing the changes in gene expression patterns in HCV-infected cells, both markers and the causes of HCV-associated liver injury may be elucidated. HCV genotype 1b virus from persistently infected VeroE6 cells induced a strong cytopathic effect when used to infect Huh7.5 hepatoma cells. To determine if this cytopathic effect was a result of apoptosis, ultrastructural changes were observed by electron microscopy and markers of programmed cell death were surveyed. Screening of a human PCR array demonstrated a gene expression profile that contained upregulated markers of apoptosis, including tumor necrosis factor, caspases and caspase activators, Fas, Bcl2-interacting killer (BIK) and tumor suppressor protein, p53, as a result of HCV genotype 1b infection. The genes identified in this study should provide new insights into understanding viral pathogenesis in liver cells and may possibly help to identify novel antiviral and antifibrotic targets.