Differential infection patterns and recent evolutionary origins of equine hepaciviruses in donkeys

Stephanie Walter, Andrea Rasche, Andrés Moreira-Soto, Stephanie Pfaender, Magda Bletsa, Victor Max Corman, Alvaro Aguilar-Setien, Fernando García-Lacy, Aymeric Hans, Daniel Todt, Gerhard Schuler, Anat Shnaiderman-Torban, Amir Steinman, Cristina Roncoroni, Vincenzo Veneziano, Nikolina Rusenova, Nikolay Sandev, Anton Rusenov, Dimitrinka Zapryanova, Ignacio García-BocanegraJoerg Jores, Augusto Carluccio, Maria Cristina Veronesi, Jessika M.V. Cavalleri, Christian Drosten, Philippe Lemey, Eike Steinmann*, Jan Felix Drexler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


The hepatitis C virus (HCV) is a major human pathogen. Genetically related viruses in animals suggest a zoonotic origin of HCV. The closest relative of HCV is found in horses (termed equine hepacivirus [EqHV]). However, low EqHV genetic diversity implies relatively recent acquisition of EqHV by horses, making a derivation of HCV from EqHV unlikely. To unravel the EqHV evolutionary history within equid sister species, we analyzed 829 donkeys and 53 mules sampled in nine European, Asian, African, and American countries by molecular and serologic tools for EqHV infection. Antibodies were found in 278 animals (31.5%), and viral RNA was found in 3 animals (0.3%), all of which were simultaneously seropositive. A low RNA prevalence in spite of high seroprevalence suggests a predominance of acute infection, a possible difference from the mostly chronic hepacivirus infection pattern seen in horses and humans. Limitation of transmission due to short courses of infection may explain the existence of entirely seronegative groups of animals. Donkey and horse EqHV strains were paraphyletic and 97.5 to 98.2% identical in their translated polyprotein sequences, making virus/host cospeciation unlikely. Evolutionary reconstructions supported host switches of EqHV between horses and donkeys without the involvement of adaptive evolution. Global admixture of donkey and horse hepaciviruses was compatible with anthropogenic alterations of EqHV ecology. In summary, our findings do not support EqHV as the origin of the significantly more diversified HCV. Identification of a host system with predominantly acute hepacivirus infection may enable new insights into the chronic infection pattern associated with HCV.

Original languageAmerican English
Article numbere01711-16
JournalJournal of Virology
Issue number1
StatePublished - 2017

Bibliographical note

Funding Information:
We thank Monika Eschbach-Bludau, Sebastian Brünink, and Tobias Bleicker (University of Bonn Medical Centre, Bonn, Germany), Michael Engelmann (Twincore, Hannover, Germany), and Rocio Gonzales Barrientos and Gabriela Hernandez Mora (SENASA Costa Rica) for assistance. We are grateful to Peter D. Burbelo (NIH, Bethesda, MD) for providing the Renilla-luciferase-NS3 fusion plasmid. S.W. was supported by the Hannover Biomedical Research School and the Centre for Infection Biology (ZIB). E.S. was supported by an intramural young investigator award from the Helmholtz Centre for Infection Research. A.M.S. was supported by a personal scholarship from the German Academic Exchange Service (DAAD). This study was funded by German Research Foundation (DFG) grants STE 1954/1-1 to E.S. and 810/1-1 to J.F.D. and an intramural grant from the University of Bonn (BONFOR) to J.F.D. TWINCORE is a joint venture between the Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© 2016 American Society for Microbiology.


  • Donkey
  • Equine hepacivirus
  • Evolution
  • Hepatitis C virus
  • Pathogenesis


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