ArticleThe Journal of biological chemistry2009
The hepatitis C virus non-structural NS5A protein impairs both the innate and adaptive hepatic immune response in vivo.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Trial
- Article
- A short hepatitis C virus NS5A peptide expression by AAV vector modulates human T cell activation and reduces vector immunogenicity.Gene therapy · 2022Article
- Hepatitis C Virus and Hepatocellular Carcinoma: When the Host Loses Its Grip.International journal of molecular sciences · 2020Review
- Interactions between Viperin, Vesicle-Associated Membrane Protein A, and Hepatitis C Virus Protein NS5A Modulate Viperin Activity and NS5A Degradation.Biochemistry · 2020Article
- Article
- Article
- The Autophagosomal SNARE Protein Syntaxin 17 Is an Essential Factor for the Hepatitis C Virus Life Cycle.Journal of virology · 2016Article
- Mapping the genomic diversity of HCV subtypes 1a and 1b: Implications of structural and immunological constraints for vaccine and drug development.Virus evolution · 2016Article
- Classical swine fever virus NS5A protein changed inflammatory cytokine secretion in porcine alveolar macrophages by inhibiting the NF-κB signaling pathway.Virology journal · 2016Article
- Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses.Scientific reports · 2016Article
- Resistance-Associated NS5A Variants of Hepatitis C Virus Are Susceptible to Interferon-Based Therapy.PloS one · 2015Article
- HCV NS5A and IRF9 compete for CypA binding.Journal of hepatology · 2013Article
- Early transcriptional programming links progression to hepatitis C virus-induced severe liver disease in transplant patients.Hepatology (Baltimore, Md.) · 2012Article
- Regulatory T cells and Th17 cells in viral infections: implications for multiple sclerosis and myocarditis.Future virology · 2012Article
- A cell-permeable hairpin peptide inhibits hepatitis C viral nonstructural protein 5A-mediated translation and virus production.Hepatology (Baltimore, Md.) · 2012Article
- Dendritic cells in hepatitis C infection: can they (help) win the battle?Journal of gastroenterology · 2011Review
- In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Induction and evasion of innate antiviral responses by hepatitis C virus.The Journal of biological chemistry · 2010Review
- Hepatitis C virus NS5A activates the mammalian target of rapamycin (mTOR) pathway, contributing to cell survival by disrupting the interaction between FK506-binding protein 38 (FKBP38) and mTOR.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of hepatitis C virus (HCV) protein non-structural (NS) 5A in HCV-associated pathogenesis is still enigmatic. To investigate the in vivo role of NS5A for viral persistence and virus-associated pathogenesis a transgenic (Tg) mouse model was established. Mice with liver-targeted NS5A transgene expression were generated using the albumin promoter. Alterations in the hepatic immune response were determined by Western blot, infection by lymphocytic choriomeningitis virus (LCMV), and using transient NS3/4A Tg mice generated by hydrodynamic injection. Cytotoxic T lymphocyte (CTL) activity was investigated by the Cr-release assay. The stable NS5A Tg mice did not reveal signs of spontaneous liver disease. The intrahepatic immunity was disrupted in the NS5A Tg mice as determined by clearance of LCMV infection or transiently NS3/4A Tg hepatocytes in vivo. This impaired immunity was explained by a reduced induction of interferon beta, 2',5'-OAS, and PKR after LCMV infection and an impairment of the CTL-mediated elimination of NS3-expressing hepatocytes. In conclusion, these data indicate that in the present transgenic mouse model, NS5A does not cause spontaneous liver disease. However, we discovered that NS5A could impair both the innate and the adaptive immune response to promote chronic HCV infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.