Treatment of hepatitis C virus core-positive hepatocytes with the transfer of recombinant caspase-3 using the 2',5'-oligoadenylate synthetase gene promoter.
Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality throughout the world. There is no vaccine available and current therapy is only partially effective. Since HCV infects only a minority of hepatocytes, we hypothesized that induction of apoptosis might be a promising approach for the treatment of hepatitis C. In the present study, recombinant caspase-3 gene (re-caspase-3) was used because it has the ability to induce apoptosis that is independent of the initiator caspases. An HCV-specific promoter is required to regulate the cytotoxic caspase-3 expression in HCV-infected cells. It has been reported that HCV core protein can specifically activate the 2',5'-oligoadenylate synthetase (OAS) gene promoter in human hepatocytes. Therefore, we constructed an expression vector consisting of the re-caspase-3 under the OAS gene promoter (pGL3-OAS-re-caspase-3) and then investigated its effect on HCV core-positive liver cells. It was found that the pGL3-OAS-re-caspase-3 construct induced apoptosis in HCV core-positive liver cells, but not in normal liver cells. These results strongly suggested that the transfer of the re-caspase-3 gene under the OAS promoter was a novel targeting approach for the treatment of HCV infection.
Wang
Ying
Y
Department of Pathology, Basic Medical College, Central South University, Changsha 410078, China.
Mao
Shanshan
S
Li
Bo
B
Tan
Pingping
P
Feng
Deyun
D
Wen
Jifang
J
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D017209:Apoptosis; D055162:Biocatalysis; D053148:Caspase 3 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000628:therapy*; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014758:Viral Core Proteins / Q000378:metabolism*
D011994:Recombinant Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D015088:2',5'-Oligoadenylate Synthetase; D053148:Caspase 3