ArticleHepatology (Baltimore, Md.)2022
Neutralization and receptor use of infectious culture-derived rat hepacivirus as a model for HCV.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Discovery of 5' NAD capped viral RNAs reveals evolutionary divergent 5' metabolite capping across hepaciviruses.Nature communications · 2026Article
- An immunocompetent murine model of virus-elicited liver fibrosis and hepatocellular carcinoma.Journal of hepatology · 2026Article
- Development of a Norway rat hepacivirus reporter for high-throughput quantification of neutralizing antibodies.Journal of virology · 2026Article
- Generation of a HiBiT-expressing recombinant rat hepacivirus supporting both in vivo and in vitro infection.PLoS pathogens · 2026Article
- Article
- Identification of claudin-3 as an entry factor for rat hepacivirus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- In vivo and in vitro recombinant systems of a novel variant demonstrate cross-reactive neutralization for the HCV model virus, Norway rat hepacivirus.PLoS pathogens · 2025Article
- Design and nonviral delivery of live attenuated vaccine to prevent chronic hepatitis C virus-like infection.Nature communications · 2025Article
- OPTIMIZATION OF HCV CELL CULTURE SYSTEM FOR EVALUATION OF ANTIVIRAL DRUGS AGAINST HCV GENOTYPES 2a AND 4a.Acta clinica Croatica · 2025Article
- GB Virus B and Hepatitis C Virus, Distantly Related Hepaciviruses, Share an Entry Factor, Claudin-1.Journal of virology · 2023Article
- Neutralization and receptor use of infectious culture-derived rat hepacivirus as a model for HCV.Hepatology (Baltimore, Md.) · 2022Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsLack of tractable immunocompetent animal models amenable to robust experimental challenge impedes vaccine efforts for HCV. Infection with rodent hepacivirus from Rattus norvegicus (RHV-rn1) in rats shares HCV-defining characteristics, including liver tropism, chronicity, and pathology. RHV in vitro cultivation would facilitate genetic studies on particle production, host factor interactions, and evaluation of antibody neutralization guiding HCV vaccine approaches. APPROACH AND
resultsWe report an infectious reverse genetic cell culture system for RHV-rn1 using highly permissive rat hepatoma cells and adaptive mutations in the E2, NS4B, and NS5A viral proteins. Cell culture-derived RHV-rn1 particles (RHVcc) share hallmark biophysical characteristics of HCV and are infectious in mice and rats. Culture adaptive mutations attenuated RHVcc in immunocompetent rats, and the mutations reverted following prolonged infection, but not in severe combined immunodeficiency (SCID) mice, suggesting that adaptive immune pressure is a primary driver of reversion. Accordingly, sera from RHVcc-infected SCID mice or the early acute phase of immunocompetent mice and rats were infectious in culture. We further established an in vitro RHVcc neutralization assay, and observed neutralizing activity of rat sera specifically from the chronic phase of infection. Finally, we found that scavenger receptor class B type I promoted RHV-rn1 entry in vitro and in vivo.
conclusionsThe RHV-rn1 infectious cell culture system enables studies of humoral immune responses against hepacivirus infection. Moreover, recapitulation of the entire RHV-rn1 infectious cycle in cell culture will facilitate reverse genetic studies and the exploration of tropism and virus-host interactions.
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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.