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Journal of virology2012; 86(11); 6171-6178; doi: 10.1128/JVI.00250-12

Serology-enabled discovery of genetically diverse hepaciviruses in a new host.

Abstract: Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest phylogenetic relative of HCV. Recombinant protein expressed from the helicase domain of CHV NS3 was used as antigen in the luciferase immunoprecipitation system (LIPS) assay to screen several nonprimate animal species. Thirty-six samples from 103 horses were immunoreactive, and viral genomic RNA was present in 8 of the 36 seropositive animals and none of the seronegative animals. Complete genome sequences of these 8 genetically diverse NPHVs showed 14% (range, 6.4% to 17.2%) nucleotide sequence divergence, with most changes occurring at synonymous sites. RNA secondary structure prediction of the 383-base 5' untranslated region of NPHV was refined and extended through mapping of polymorphic sites to unpaired regions or (semi)covariant pairings. Similar approaches were adopted to delineate extensive RNA secondary structures in the coding region of the genome, predicted to form 27 regularly spaced, thermodynamically stable stem-loops. Together, these findings suggest a promising new nonprimate animal model and provide a database that will aid creation of functional NPHV cDNA clones and other novel tools for hepacivirus studies.
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Publication Date: 2012-04-04 PubMed ID: 22491452PubMed Central: PMC3372197DOI: 10.1128/JVI.00250-12Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • N.I.H.
  • Intramural
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigated new hepaciviruses found in animals to further our understanding of Hepatitis C virus (HCV) and its origins in humans. The study identified these viruses’ natural hosts and revealed a significant genetic diversity among them, contributing to our capacity to study their pathogenesis using an animal model.

Research Objective

  • The aim of the study was to understand the origins of Hepatitis C virus (HCV) in humans by analyzing new hepaciviruses in animals. This was achieved through determining the natural host for the nonprimate hepacivirus (NPHV), a recent canine hepacivirus(CHV).

Methodology

  • The researchers utilized a luciferase immunoprecipitation system (LIPS) assay with a recombinant protein created from the CHV NS3 helicase domain as an antigen. This method was used to screen several nonprimate animal species for the presence of the virus.
  • The study verified the presence of hepacivirus in horse blood samples, with viral genomic RNA detected in eight out of the 36 immunoreactive samples. No viral genetic material was detected in seronegative samples.

Findings

  • The research revealed a 14% nucleotide sequence divergence in the complete genome sequences of the eight genetically diverse NPHVs found in the seropositive samples. The changes primarily occurred at synonymous sites.
  • Additionally, predictions of RNA secondary structure of the NPHV were refined through mapping polymorphism sites to unpaired regions or (semi)covariant pairings.
  • The research also delineated extensive RNA secondary structures in the genome coding region, predicted to form 27 regularly spaced, stable stem-loops.

Implications

  • The research findings offer a new nonprimate animal model to study the origins and pathogenesis of HCV. The genetic diversity observed among the hepaciviruses broadens our understanding of this kind of virus.
  • The data obtained will enable the creation of functional NPHV cDNA clones and other innovative tools for hepacivirus studies, opening up new potential directions for future research.

Cite This Article

APA
Burbelo PD, Dubovi EJ, Simmonds P, Medina JL, Henriquez JA, Mishra N, Wagner J, Tokarz R, Cullen JM, Iadarola MJ, Rice CM, Lipkin WI, Kapoor A. (2012). Serology-enabled discovery of genetically diverse hepaciviruses in a new host. J Virol, 86(11), 6171-6178. https://doi.org/10.1128/JVI.00250-12

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 86
Issue: 11
Pages: 6171-6178

Researcher Affiliations

Burbelo, Peter D
  • Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
Dubovi, Edward J
    Simmonds, Peter
      Medina, Jan L
        Henriquez, Jose A
          Mishra, Nischay
            Wagner, Jason
              Tokarz, Rafal
                Cullen, John M
                  Iadarola, Michael J
                    Rice, Charles M
                      Lipkin, W Ian
                        Kapoor, Amit

                          MeSH Terms

                          • 5' Untranslated Regions
                          • Animals
                          • Antigens, Viral / genetics
                          • Hepacivirus / genetics
                          • Hepacivirus / immunology
                          • Hepacivirus / pathogenicity
                          • Hepatitis C / immunology
                          • Hepatitis C / veterinary
                          • Hepatitis C Antibodies / blood
                          • Horse Diseases / virology
                          • Horses
                          • Host Specificity
                          • Molecular Sequence Data
                          • Nucleic Acid Conformation
                          • RNA, Viral / genetics
                          • Recombinant Proteins / genetics
                          • Sequence Analysis, DNA

                          Grant Funding

                          • R21 AI081132 / NIAID NIH HHS
                          • AI070411 / NIAID NIH HHS
                          • U01 AI070411 / NIAID NIH HHS
                          • R24 EY017404 / NEI NIH HHS
                          • 095831 / Wellcome Trust
                          • U54 AI057158 / NIAID NIH HHS
                          • Intramural NIH HHS
                          • AI081132 / NIAID NIH HHS
                          • EY017404 / NEI NIH HHS
                          • R21 AI090196 / NIAID NIH HHS
                          • R01 AI079231 / NIAID NIH HHS
                          • AI57158 / NIAID NIH HHS
                          • AI079231 / NIAID NIH HHS
                          • AI090196 / NIAID NIH HHS

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                          This article has been cited 139 times.
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