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Int J Infect Dis. 2014 Aug;25:38-44. doi: 10.1016/j.ijid.2014.01.010. Epub 2014 May 17.

Studies on the role of NS3 and NS5A non-structural genes of hepatitis C virus genotype 3a local isolates in apoptosis.

Author information

1
Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.
2
National Center of Excellence in Molecular Biology, University of the Punjab, 87 West Canal Bank Road, Thokar Niaz Baig, Lahore 53700, Pakistan. Electronic address: Idrees.khan96@yahoo.com.
3
Center of Applied Molecular Biology, Ministry of Science and Technology, Govt. of Punjab, Lahore, Pakistan.
4
Department of Biotechnology, University of Malakand, Chakdra Dir (lower), Khyber Pakhtunkhwa, Pakistan.

Abstract

BACKGROUND:

Hepatitis C virus (HCV) is the causative agent of chronic liver diseases, which usually lead to liver fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Among the non-structural genes of HCV, NS3 and NS5A play important roles in apoptosis. The NS3 and NS5A genes of HCV interact with the p53 tumor suppressor gene differentially. The objective of this study was to analyze the interaction of NS3 and NS5A genes of HCV genotype 3a with the p53 gene, subgenomic HCV replicons harboring NS3 and NS5A genes.

METHODS:

Huh-7 cell lines stably expressing NS3 and NS5A genes were generated. The stable cell lines were confirmed by Western blot, reverse transcriptase PCR, and immunofluorescence assay. HCV NS3- and NS5A-expressing cell lines were transfected with p53-expressing clone.

RESULTS:

NS3 and NS5A both interact with p53 by down-regulating the expression of the p53 gene. In HCV subgenomic harboring cells, the interaction of NS3 and NS5A with p53 was observed consistently. The suppression of p53 gene expression by NS3 and NS5A was observed significantly as compared with NS3- and NS5A-negative control Huh-7 cells.

CONCLUSION:

It is concluded that both of the non-structural genes, NS3 and NS5A, of HCV play important roles in the hepatocarcinogenesis of HCV by interacting directly or indirectly in different manners with the p53 gene.

KEYWORDS:

HCC; Hepatitis C virus; Huh-7 cell lines; Liver cirrhoses; Non-structural proteins; p53 gene

PMID:
24845365
DOI:
10.1016/j.ijid.2014.01.010
[Indexed for MEDLINE]
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