HCV-Mediated Apoptosis of Hepatocytes in Culture and Viral Pathogenesis.
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.
Laboratory of Emerging Pathogens, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER FDA, Silver Spring, MD, 20903, United States of America.
Erica
E
Silberstein
Laboratory of Emerging Pathogens, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER FDA, Silver Spring, MD, 20903, United States of America.
Laura
L
Ulitzky
Laboratory of Emerging Pathogens, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER FDA, Silver Spring, MD, 20903, United States of America.
Livia Alves
LA
Lima
Laboratory of Emerging Pathogens, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER FDA, Silver Spring, MD, 20903, United States of America.
Nicoleta
N
Cehan
Laboratory of Emerging Pathogens, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER FDA, Silver Spring, MD, 20903, United States of America.
Andréa
A
Teixeira-Carvalho
INSERM U966, Universite Francois Rabelais and CHRU de Tours, Tours, France.
Philippe
P
Roingeard
Laboratory of Emerging Pathogens, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, CBER FDA, Silver Spring, MD, 20903, United States of America.
Deborah R
DR
Taylor
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins