ArticleProceedings of the National Academy of Sciences of the United States of America2015
Characterization of nonprimate hepacivirus and construction of a functional molecular clone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- Evaluation of mosquito transmission of equine hepacivirus in laboratory and field studies.Journal of medical entomology · 2026Article
- 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
- Chronic hepatitis in horses with persistent equine hepacivirus infection.Equine veterinary journal · 2026Article
- Identification and Long-Term Detection ofViruses · 2026Article
- First Detection and Phylogenetic Analysis of Equine Hepacivirus (EqHV) in Iran.Veterinary medicine and science · 2026Article
- Natural Hepacivirus Infection in Tree Shrews: A Call for Routine Screening in Hepatitis Virus Research.Viruses · 2025Article
- Evaluation of Risk Determinants and Molecular Characterisation for Non-Primate Hepacivirus Infection in Turkish Horses.Pathogens (Basel, Switzerland) · 2025Article
- A key role for hepatitis C virus NS5A serine 225 phosphorylation revealed by super-resolution microscopy.Scientific reports · 2025Article
- Detection of Equine Parvovirus-Hepatitis Virus and Equine Hepacivirus in Archived Sera from Horses in France and Australia.Viruses · 2024Article
- Naturally acquired equine parvovirus-hepatitis is associated with a wide range of hepatic lesions in horses.Veterinary pathology · 2024Article
- Article
- Review
- European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe.Journal of veterinary internal medicine · 2022Article
- Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response.Microbiology spectrum · 2022Article
- Equine Hepacivirus: A Systematic Review and a Meta-Analysis of Serological and Biomolecular Prevalence and a Phylogenetic Update.Animals : an open access journal from MDPI · 2022Review
- MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication.Pathogens (Basel, Switzerland) · 2022Review
- Article
- Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.Virus evolution · 2022Article
- Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.Hepatology (Baltimore, Md.) · 2021Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼ 3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3'-UTR was determined and consists of interspersed homopolymer tracts and an HCV-like 3'-terminal poly(U)-X-tail. NPHV translation is stimulated by miR-122 and the 3'-UTR and, similar to HCV, the NPHV NS3-4A protease can cleave mitochondrial antiviral-signaling protein to inactivate the retinoic acid-inducible gene I pathway. Using an NPHV consensus cDNA clone, replication was not observed in primary equine fetal liver cultures or after electroporation of selectable replicons. However, intrahepatic RNA inoculation of a horse initiated infection, yielding high RNA titers in the serum and liver. Delayed seroconversion, slightly elevated circulating liver enzymes and mild hepatitis was observed, followed by viral clearance. This establishes the molecular components of a functional NPHV genome. Thus, NPHV appears to resemble HCV not only in genome structure but also in its ability to establish chronic infection with delayed seroconversion and hepatitis. This NPHV infectious clone and resulting acute phase sera will facilitate more detailed studies on the natural history, pathogenesis, and immunity of this novel hepacivirus in its natural host.
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