ArticleJournal of virology2004
Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- Hepatitis C and non-Hodgkin lymphoma among 4784 cases and 6269 controls from the International Lymphoma Epidemiology Consortium.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2008Pooled it
- Mechanisms and Therapeutic Strategies for HCV/HBV-Associated B-Cell Non-Hodgkin's Lymphomas: A Viewpoint.Oncology research · 2026Review
- Defence Warriors: Exploring the crosstalk between polyamines and oxidative stress during microbial pathogenesis.Redox biology · 2025Review
- B Cell Differentiation and the Origin and Pathogenesis of Human B Cell Lymphomas.Methods in molecular biology (Clifton, N.J.) · 2025Review
- From viruses to cancer: exploring the role of the hepatitis C virus NS3 protein in carcinogenesis.Infectious agents and cancer · 2024Review
- Carcinogenic mechanisms of virus-associated lymphoma.Frontiers in immunology · 2024Review
- SARS-CoV-2 and the DNA damage response.The Journal of general virology · 2023Review
- Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies.Journal of clinical and translational hepatology · 2023Review
- Associations of Head and Neck Cancer with Hepatitis B Virus and Hepatitis C Virus Infection.Cancers · 2023Article
- Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis C Virus Infection.Biology · 2022Review
- DNA methylation at hepatitis B virus integrants and flanking host mitochondrially encoded cytochrome C oxidase III.Oncology letters · 2022Article
- Review
- Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-γH2AX Signaling Pathways to Foster Its Replication.Viruses · 2022Article
- Second malignant neoplasms in lymphomas, secondary lymphomas and lymphomas in metabolic disorders/diseases.Cell & bioscience · 2022Review
- Oxidative Stress-Related Mechanisms in SARS-CoV-2 Infections.Oxidative medicine and cellular longevity · 2022Review
- HCV and tumor-initiating stem-like cells.Frontiers in physiology · 2022Review
- Nitric Oxide to Fight Viral Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- High Seroprevalence of Hepatitis C Virus Antibody in Breast Cancer Patients in Egypt.Breast cancer : basic and clinical research · 2021Article
- Hepatitis C virus and carpal tunnel syndrome in hemodialysis patients: a single center cross-sectional study.Renal failure · 2020Observational
- NADSignal transduction and targeted therapy · 2020Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) infection causes hepatitis, hepatocellular carcinoma, and B-cell lymphomas in a significant number of patients. Previously we have shown that HCV infection causes double-stranded DNA breaks and enhances the mutation frequency of cellular genes, including proto-oncogenes and immunoglobulin genes. To determine the mechanisms, we studied in vitro HCV infection of cell culture. Here we report that HCV infection activated the immunologic (type II) isoform of nitric oxide (NO) synthase (NOS), i.e., inducible NOS (iNOS), thereby inducing NO, which in turn induced DNA breaks and enhanced the mutation frequencies of cellular genes. Treatment of HCV-infected cells with NOS inhibitors or small interfering RNA specific for iNOS abolished most of these effects. Expression of the core protein or nonstructural protein 3 (NS3), but not the other viral proteins, in B cells or hepatocytes induced iNOS and DNA breaks, which could be blocked by NOS inhibitors. The core protein also enhanced the mutation frequency of cellular genes in hepatocytes derived from HCV core transgenic mice compared with that in control mice. The iNOS promoter was activated more than fivefold in HCV-infected cells, as revealed by a luciferase reporter assay driven by the iNOS promoter. Similarly, the core and NS3 proteins also induced the same effects. Therefore, we conclude that HCV infection can stimulate the production of NO through activation of the gene for iNOS by the viral core and NS3 proteins. NO causes DNA breaks and enhances DNA mutation. This sequence of events provides a mechanism for HCV pathogenesis and oncogenesis.
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