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Home / Equine Research Bank / PLoS Pathog / Evidence for novel hepaciviruses in rodents.
PLoS pathogens2013; 9(6); e1003438; doi: 10.1371/journal.ppat.1003438

Evidence for novel hepaciviruses in rodents.

Abstract: Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.
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Publication Date: 2013-06-20 PubMed ID: 23818848PubMed Central: PMC3688547DOI: 10.1371/journal.ppat.1003438Google Scholar: Lookup
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Summary

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The study reveals the discovery of new hepaciviruses in rodents that could improve the understanding of hepatitis C virus (HCV) evolution and help in developing small animal models for HCV research.

Study Methodology and Sample Collection

  • Researchers gathered the largest collection of small-mammal samples from around the world which can be screened for bloodborne viruses. These include sera and organs from 4,770 rodents, belonging to 41 species, and sera from 2,939 bats, from 51 species.
  • Additionally, 210 horses and 858 cats and dogs were tested.

Identification of Novel Hepaciviruses in Rodents

  • The team identified three highly divergent rodent hepacivirus clades in 1.8% of 1,465 European bank voles and 1.9% of 518 South African four-striped mice tested.
  • These rodent viruses were found to be as diverse from HCV as HCV is from the existing hepaciviruses, expanding the known diversity of this viral group.
  • Bats’ immunoblot reactivities suggested genetic relatedness to HCV but no viruses were detected. This indicates limitations in the current detection methods or low viral RNA concentrations.
  • Horse-associated hepaciviruses were also identified, but none were found in cats or dogs.

Genome Features and Classification

  • Five full genomes, representing all viral lineages, were sequenced.
  • Based on genome features and distance criteria, all viruses were classified as hepaciviruses.

Disease Characteristics and Seroprevalence Rates

  • Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested a hepatic tropism – the viruses seemed to preferentially infect the liver and caused inflammation similar to that seen in chronic hepatitis C in humans.
  • Serology for two distinct hepacivirus lineages showed prevalence rates of 8.3 and 12.4% in bank voles.
  • However, antibodies in the voles’ sera didn’t cross-react with HCV nor the different hepacivirus in the bank vole, indicating distinct immunological responses or variations.
  • The presence of both virus and antibodies together was observed in 5.3% of PCR-positive bank vole sera.

Implications of the Research

  • The findings shed light on potential new hypotheses about the evolution of HCV and can provide invaluable insight to virus researchers.
  • The discovery further encourages the development of rodent models for HCV, facilitating more accessible research options considering the high relevance of HCV as a cause of liver disease and cancer.

Cite This Article

APA
Drexler JF, Corman VM, Müller MA, Lukashev AN, Gmyl A, Coutard B, Adam A, Ritz D, Leijten LM, van Riel D, Kallies R, Klose SM, Gloza-Rausch F, Binger T, Annan A, Adu-Sarkodie Y, Oppong S, Bourgarel M, Rupp D, Hoffmann B, Schlegel M, Kümmerer BM, Krüger DH, Schmidt-Chanasit J, Setién AA, Cottontail VM, Hemachudha T, Wacharapluesadee S, Osterrieder K, Bartenschlager R, Matthee S, Beer M, Kuiken T, Reusken C, Leroy EM, Ulrich RG, Drosten C. (2013). Evidence for novel hepaciviruses in rodents. PLoS Pathog, 9(6), e1003438. https://doi.org/10.1371/journal.ppat.1003438

Publication

PLoS pathogens
ISSN: 1553-7374
NlmUniqueID: 101238921
Country: United States
Language: English
Volume: 9
Issue: 6
Pages: e1003438

Researcher Affiliations

Drexler, Jan Felix
  • Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Corman, Victor Max
    Müller, Marcel Alexander
      Lukashev, Alexander N
        Gmyl, Anatoly
          Coutard, Bruno
            Adam, Alexander
              Ritz, Daniel
                Leijten, Lonneke M
                  van Riel, Debby
                    Kallies, Rene
                      Klose, Stefan M
                        Gloza-Rausch, Florian
                          Binger, Tabea
                            Annan, Augustina
                              Adu-Sarkodie, Yaw
                                Oppong, Samuel
                                  Bourgarel, Mathieu
                                    Rupp, Daniel
                                      Hoffmann, Bernd
                                        Schlegel, Mathias
                                          Kümmerer, Beate M
                                            Krüger, Detlev H
                                              Schmidt-Chanasit, Jonas
                                                Setién, Alvaro Aguilar
                                                  Cottontail, Veronika M
                                                    Hemachudha, Thiravat
                                                      Wacharapluesadee, Supaporn
                                                        Osterrieder, Klaus
                                                          Bartenschlager, Ralf
                                                            Matthee, Sonja
                                                              Beer, Martin
                                                                Kuiken, Thijs
                                                                  Reusken, Chantal
                                                                    Leroy, Eric M
                                                                      Ulrich, Rainer G
                                                                        Drosten, Christian

                                                                          MeSH Terms

                                                                          • Animals
                                                                          • Base Sequence
                                                                          • Cats
                                                                          • Dogs
                                                                          • Evolution, Molecular
                                                                          • Genome, Viral
                                                                          • Hepacivirus / genetics
                                                                          • Hepacivirus / metabolism
                                                                          • Hepatitis C / blood
                                                                          • Hepatitis C / genetics
                                                                          • Hepatitis C / virology
                                                                          • Hepatitis C Antibodies / blood
                                                                          • Hepatitis, Animal / blood
                                                                          • Hepatitis, Animal / genetics
                                                                          • Hepatitis, Animal / virology
                                                                          • Horses
                                                                          • Molecular Sequence Data
                                                                          • RNA, Viral / blood
                                                                          • RNA, Viral / genetics
                                                                          • Rodentia / blood
                                                                          • Rodentia / virology

                                                                          Conflict of Interest Statement

                                                                          The authors have declared that no competing interests exist.

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