Expression of hepatitis C virus core protein impairs DNA repair in human hepatoma cells.
Several studies have documented the important association between hepatitis C virus (HCV) infection and hepatocellular carcinoma. The mechanisms involved are still unknown and could involve viral proteins. We investigated the effect of HCV-core protein on DNA repair after UV-induced DNA damage. Therefore, we developed and characterized stably transfected HepG2 cell lines that express HCV-core protein as demonstrated by immunohistochemistry. These cells were significantly less capable to repair the DNA damage than control cells. This suppression of DNA repair by HCV-core protein renders the cells more sensitive to acquire mutations that in combination with enhanced in vivo cell turnover in the infected liver might increase the likelihood of malignant transformation of HCV-infected cells by other viral factors or upon exposure to environmental factors (food, drugs, smoking, alcohol, etc.). Interestingly, expression of the full-length HCV core did increase the cell doubling time in one of the cell lines we had developed that could not be attributed to an increase in apoptosis or change in telomerase activity in these cells.
van Pelt
Jos F
JF
Department of Liver and Pancreatic Diseases, University Hospital Gasthuisberg, Herestraat 49, Leuven B 3000, Belgium. jos.vanpelt@med.kuleuven.ac.be
Severi
Tamara
T
Crabbé
Tina
T
Eetveldt
Annemie Van
AV
Verslype
Chris
C
Roskams
Tania
T
Fevery
Johan
J
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D018936:Hepatitis C Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D018936:Hepatitis C Antigens; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D019098:Telomerase