Hepatitis C virus protein expression induces apoptosis in HepG2 cells.
The mechanisms of hepatocyte death and the events that lead to a high rate of chronic liver disease in patients infected with hepatitis C virus are not known. We established a HCV replication system in HepG2 cell culture and utilized this model to address the effect of HCV proteins on HepG2 cell growth and viability. After transfection of HepG2 cells with full-length RNA, a truncated RNA, or an antisense RNA, cell proliferation and cell viability were analyzed by thymidine uptake and the trypan blue exclusion method, respectively. Full-length RNA transfected HepG2 cells showed a decrease in cell proliferation and viability compared to cells transfected with HCV truncated RNA and antisense RNA control. A subset of cells expressing HCV proteins underwent apoptosis as documented by morphological studies, ultrastructural analysis, cell cycle analysis by flow cytometry, terminal transferase enzyme mediated end labeling of DNA, and DNA laddering. This study suggests that expression of HCV proteins can lead to cell death by apoptosis, which may be an important event in the pathogenesis of chronic hepatitis C virus infection in humans.
Kalkeri
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Department of Pathology and Laboratory Medicine, Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
Khalap
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Garry
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Fermin
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Dash
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D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D005434:Flow Cytometry; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D009154:Mutation; D016372:RNA, Antisense / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
D016372:RNA, Antisense; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D004247:DNA; D013936:Thymidine