title: Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys.
abstract: 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.
  
  
  OBJECTIVE
  The evolutionary origins of the human hepatitis C virus (HCV) are unclear. The closest animal-associated relative of HCV occurs in horses (equine hepacivirus [EqHV]). The low EqHV genetic diversity implies a relatively recent acquisition of EqHV by horses, limiting the time span for potential horse-to-human infections in the past. Horses are genetically related to donkeys, and EqHV may have cospeciated with these host species. Here, we investigated a large panel of donkeys from various countries using serologic and molecular tools. We found EqHV to be globally widespread in donkeys and identify potential differences in EqHV infection patterns, with donkeys potentially showing enhanced EqHV clearance compared to horses. We provide strong evidence against EqHV cospeciation and for its capability to switch hosts among equines. Differential hepacivirus infection patterns in horses and donkeys may enable new insights into the chronic infection pattern associated with HCV.
authors: Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
authors: Stephanie
authors: S
authors: Walter
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.|German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
authors: Andrea
authors: A
authors: Rasche
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors: Andrés
authors: A
authors: Moreira-Soto
authors: Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
authors: Stephanie
authors: S
authors: Pfaender
authors: Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
authors: Magda
authors: M
authors: Bletsa
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.|German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
authors: Victor Max
authors: VM
authors: Corman
authors: Medical Immunology Research Unit, National Medical Center Siglo XXL, Mexican Social Security Institute (IMSS), Mexico City, Mexico.
authors: Alvaro
authors: A
authors: Aguilar-Setien
authors: Equine Medicine and Surgery Department FMVZ-UNAM, Mexico City, Mexico.
authors: Fernando
authors: F
authors: García-Lacy
authors: ANSES, Laboratory for Equine Diseases, Goustranville, France.
authors: Aymeric
authors: A
authors: Hans
authors: Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
authors: Daniel
authors: D
authors: Todt
authors: Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus-Liebig-Universität Giessen, Giessen, Germany.
authors: Gerhard
authors: G
authors: Schuler
authors: Koret School of Veterinary Medicine, Rehovot, Israel.
authors: Anat
authors: A
authors: Shnaiderman-Torban
authors: Koret School of Veterinary Medicine, Rehovot, Israel.
authors: Amir
authors: A
authors: Steinman
authors: Istituto Zooprofilattico Sperimentale Lazio e Toscana, Rome, Italy.
authors: Cristina
authors: C
authors: Roncoroni
authors: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors: Vincenzo
authors: V
authors: Veneziano
authors: Trakia University, Faculty of Veterinary Medicine, Department of Veterinary Microbiology, Infectious and Parasitic Diseases, Stara Zagora, Bulgaria.
authors: Nikolina
authors: N
authors: Rusenova
authors: Trakia University, Faculty of Veterinary Medicine, Department of Veterinary Microbiology, Infectious and Parasitic Diseases, Stara Zagora, Bulgaria.
authors: Nikolay
authors: N
authors: Sandev
authors: Trakia University, Faculty of Veterinary Medicine, Department of Internal Diseases, Stara Zagora, Bulgaria.
authors: Anton
authors: A
authors: Rusenov
authors: Trakia University, Faculty of Veterinary Medicine, Department of Pharmacology, Veterinary Physiology, and Physiological Chemistry, Stara Zagora, Bulgaria.
authors: Dimitrinka
authors: D
authors: Zapryanova
authors: Department of Animal Health, University of Córdoba, Córdoba, Spain.
authors: Ignacio
authors: I
authors: García-Bocanegra
authors: International Livestock Research Institute, Nairobi, Kenya.|Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland.
authors: Joerg
authors: J
authors: Jores
authors: Faculty of Veterinary Medicine, Università degli Studi di Teramo, Teramo, Italy.
authors: Augusto
authors: A
authors: Carluccio
authors: Department of Veterinary Medicine, Università degli Studi di Milano, Milan, Italy.
authors: Maria Cristina
authors: MC
authors: Veronesi
authors: Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
authors: Jessika M V
authors: JMV
authors: Cavalleri
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.|German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
authors: Christian
authors: C
authors: Drosten
authors: Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
authors: Philippe
authors: P
authors: Lemey
authors: Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany Eike.Steinmann@twincore.de drexler@virology-bonn.de.
authors: Eike
authors: E
authors: Steinmann
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany Eike.Steinmann@twincore.de drexler@virology-bonn.de.|German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
authors: Jan Felix
authors: JF
authors: Drexler
mesh_terms: D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D005075:Biological Evolution; D018397:Equidae; D005060:Europe / Q000453:epidemiology; D014644:Genetic Variation; D016679:Genome, Viral; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000453:epidemiology* / Q000635:transmission / Q000662:veterinary* / Q000821:virology; D006736:Horses; D058507:Host Specificity; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007630:Kenya / Q000453:epidemiology; D007843:Latin America / Q000453:epidemiology; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016036:Seroepidemiologic Studies
chemical_list: D000914:Antibodies, Viral
keywords: donkey; equine hepacivirus; evolution; hepatitis C virus; pathogenesis