The Epstein⁻Barr virus (EBV) BZLF1, the high-risk human papillomavirus (HPV) E6, and the hepatitis C virus (HCV) NS5 proteins have shown to directly bind to and degrade p53.
Association of C-myc and p53 Gene Expression and Polymorphisms with Hepatitis C (HCV) Chronic Infection, Cirrhosis and Hepatocellular Carcinoma (HCC) Stages in
HCV core modulates its own protein level via a negative feedback loop involving p53 and PA28γ to control HCV replication in p53-positive hepatocytes, which may help HCV evade immune responses and establish chronic infection.
It is our novel finding that FUSE binding protein 1 (FBP1) strongly inhibits the function of tumor suppressor p53 and is an essential host cell factor required for HCV replication.
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.
In summary, we identified a novel TP53 microindel in HCC, and provided evidence of HCC characterized by HCV infections typically associated with mutational inactivation of the TP53 gene.
Previous data from in vitro HCV-infected B-cell lines and peripheral blood mononuclear cells from HCV-positive individuals suggested that HCV might have a direct mutagenic effect on B cells, inducing mutations in the tumor suppressor gene TP53 and the proto-oncogenes BCL6 and CTNNB1 (β-catenin).
An association between p53 and ISGs expression was shown for the first time in HCV-infected patients, further supporting the contribution of p53 to host antiviral response.
The prevalence of hepatitis B surface antigen, hepatitis C antibody and aflatoxin-associated 249(ser) TP53 mutations among HCC patients was 60, 20 and 38% respectively.
The oncogenic role of NS5A of hepatitis C virus is mediated by up-regulation of survivin gene expression in the hepatocellular cell through p53 and NF-κB pathways.
It is worth noting that all human oncogenic viruses, including human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus (EBV), human herpesviruses-8/Kaposi sarcoma herpesvirus (HHV-8/KSHV) and human T-cell lymphotropic virus type 1 (HTLV-1), are capable of both inducing cell fusion and inhibiting the functions of p53 as well as pRb.
Taken together, these results suggest that DHCR24 is elevated in response to HCV infection and inhibits the p53 stress response by stimulating the accumulation of the MDM2-p53 complex in the cytoplasm and by inhibiting the acetylation of p53 in the nucleus.
The expression of p53 protein were analysed by immunocytochemistry in liver biopsies from adult patients with chronic, long-lasting hepatitis C. In order to detect TP53 mutations, PCR/SSCP and sequencing were performed.
Our results collectively suggest the possibility that NS3 plays an important role in the hepatocarcinogenesis of HCV by interacting differentially with p53 in an NS3 sequence-dependent manner.