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.
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This study investigates the evolutionary history and infection patterns of equine hepaciviruses (EqHV), particularly in donkeys, to gain insights into the origins of the hepatitis C virus (HCV) in humans. The scientists found EqHV to be prevalent in donkeys worldwide, with potential differences in infection patterns. The results, however, refute that EqHV cospeciates with its hosts or acts as a direct source of HCV.
Research Context
HCV is a major human pathogen, with genetically related viruses found in animals. The closest relative to HCV is the EqHV, making it possible that HCV has a zoonotic origin.
A lack of genetic diversity in EqHV suggests that horses, primary carriers of EqHV, may have acquired it relatively recently. This makes the derivation of HCV from EqHV unlikely, pointing towards the need to understand EqHV’s evolutionary history.
Donkeys, closely related to horses, were analyzed in this study as a possibly overlooked reservoir of the virus.
The primary goal of the research was to discern if the HCV could have evolved from the EqHV, and to understand the patterns of EqHV infection within the equid population.
Research Methodology
In this study, a total of 829 donkeys and 53 mules from across nine countries in Africa, Asia, Europe, and America were analyzed using molecular and serologic examination methods.
The scientists looked for the presence of EqHV infection by identifying antibodies (suggesting past infection) and viral RNA (indicating current infection).
The study sought to uncover possible differences in the hepacivirus infection pattern seen in horses and humans, which is mostly chronic, as compared to the potential predominance of acute infection in donkeys.
Research Findings
Findings showed that antibodies were found in 31.5% of the sampled animals, but viral RNA was found only in 0.3%, all of which were already seropositive, hinting at predominantly past and not persistent infections.
The low prevalence of RNA, but high seroprevalence, suggests that infection is largely acute in donkeys, potentially distinguishing them from horses and humans.
Donkey and horse EqHV strains were found to be 97.5 to 98.2% identical, making virus/host cospeciation, or parallel evolution of viruses and hosts, unlikely.
The study also suggested that EqHV may have migrated between horses and donkeys without undergoing adaptive evolution.
The global presence of donkey and horse hepaciviruses may be influenced by human-mediated factors.
The significantly lower diversity seen in EqHV compared to HCV suggests that EqHV may not be the origin of HCV-
Significance of the Study
The identification of potentially different infection patterns in donkeys, where hepacivirus infection seems to be predominantly acute rather than chronic, could enable new insights into the chronic infection pattern seen with HCV.
The study also refutes the co-evolution of EqHV with its host species and dismisses EqHV as the source of the more diversified HCV, which could have implications on related future investigations.
Cite This Article
APA
Walter S, Rasche A, Moreira-Soto A, Pfaender S, Bletsa M, Corman VM, Aguilar-Setien A, García-Lacy F, Hans A, Todt D, Schuler G, Shnaiderman-Torban A, Steinman A, Roncoroni C, Veneziano V, Rusenova N, Sandev N, Rusenov A, Zapryanova D, García-Bocanegra I, Jores J, Carluccio A, Veronesi MC, Cavalleri JMV, Drosten C, Lemey P, Steinmann E, Drexler JF.
(2016).
Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys.
J Virol, 91(1), e01711-16.
https://doi.org/10.1128/JVI.01711-16
Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
Rasche, Andrea
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
Moreira-Soto, Andrés
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
Pfaender, Stephanie
Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
Bletsa, Magda
Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
Corman, Victor Max
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
Aguilar-Setien, Alvaro
Medical Immunology Research Unit, National Medical Center Siglo XXL, Mexican Social Security Institute (IMSS), Mexico City, Mexico.
García-Lacy, Fernando
Equine Medicine and Surgery Department FMVZ-UNAM, Mexico City, Mexico.
Hans, Aymeric
ANSES, Laboratory for Equine Diseases, Goustranville, France.
Todt, Daniel
Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany.
Schuler, Gerhard
Clinic for Obstetrics, Gynecology and Andrology of Large and Small Animals, Justus-Liebig-Universität Giessen, Giessen, Germany.
Shnaiderman-Torban, Anat
Koret School of Veterinary Medicine, Rehovot, Israel.
Steinman, Amir
Koret School of Veterinary Medicine, Rehovot, Israel.
Roncoroni, Cristina
Istituto Zooprofilattico Sperimentale Lazio e Toscana, Rome, Italy.
Veneziano, Vincenzo
Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
Rusenova, Nikolina
Trakia University, Faculty of Veterinary Medicine, Department of Veterinary Microbiology, Infectious and Parasitic Diseases, Stara Zagora, Bulgaria.
Sandev, Nikolay
Trakia University, Faculty of Veterinary Medicine, Department of Veterinary Microbiology, Infectious and Parasitic Diseases, Stara Zagora, Bulgaria.
Rusenov, Anton
Trakia University, Faculty of Veterinary Medicine, Department of Internal Diseases, Stara Zagora, Bulgaria.
Zapryanova, Dimitrinka
Trakia University, Faculty of Veterinary Medicine, Department of Pharmacology, Veterinary Physiology, and Physiological Chemistry, Stara Zagora, Bulgaria.
García-Bocanegra, Ignacio
Department of Animal Health, University of Córdoba, Córdoba, Spain.
Jores, Joerg
International Livestock Research Institute, Nairobi, Kenya.
Institute of Veterinary Bacteriology, University of Bern, Bern, Switzerland.
Carluccio, Augusto
Faculty of Veterinary Medicine, Università degli Studi di Teramo, Teramo, Italy.
Veronesi, Maria Cristina
Department of Veterinary Medicine, Università degli Studi di Milano, Milan, Italy.
Cavalleri, Jessika M V
Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Drosten, Christian
Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
German Centre for Infection Research (DZIF), Bonn-Cologne, Germany.
Lemey, Philippe
Department of Microbiology and Immunology, Rega Institute, KU Leuven-University of Leuven, Leuven, Belgium.
Steinmann, Eike
Institute of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research Hannover, Hannover, Germany Eike.Steinmann@twincore.de drexler@virology-bonn.de.
Drexler, Jan Felix
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.
MeSH Terms
Acute Disease
Animals
Antibodies, Viral / blood
Biological Evolution
Equidae
Europe / epidemiology
Genetic Variation
Genome, Viral
Hepacivirus / classification
Hepacivirus / genetics
Hepacivirus / immunology
Hepatitis C / epidemiology
Hepatitis C / transmission
Hepatitis C / veterinary
Hepatitis C / virology
Horses
Host Specificity
Humans
Israel / epidemiology
Kenya / epidemiology
Latin America / epidemiology
Phylogeny
Sequence Analysis, DNA
Seroepidemiologic Studies
References
This article includes 57 references
. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.. Lancet 2015 Aug 22;386(9995):743-800.
Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource.. Hepatology 2014 Jan;59(1):318-27.
Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E. Global distribution and prevalence of hepatitis C virus genotypes.. Hepatology 2015 Jan;61(1):77-87.
Magiorkinis G, Magiorkinis E, Paraskevis D, Ho SY, Shapiro B, Pybus OG, Allain JP, Hatzakis A. The global spread of hepatitis C virus 1a and 1b: a phylodynamic and phylogeographic analysis.. PLoS Med 2009 Dec;6(12):e1000198.
Markov PV, Pepin J, Frost E, Deslandes S, Labbé AC, Pybus OG. Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa.. J Gen Virol 2009 Sep;90(Pt 9):2086-96.
Scheel TK, Simmonds P, Kapoor A. Surveying the global virome: identification and characterization of HCV-related animal hepaciviruses.. Antiviral Res 2015 Mar;115:83-93.
Makuwa M, Souquière S, Telfer P, Leroy E, Bourry O, Rouquet P, Clifford S, Wickings EJ, Roques P, Simon F. Occurrence of hepatitis viruses in wild-born non-human primates: a 3 year (1998-2001) epidemiological survey in Gabon.. J Med Primatol 2003 Dec;32(6):307-14.
Thézé J, Lowes S, Parker J, Pybus OG. Evolutionary and Phylogenetic Analysis of the Hepaciviruses and Pegiviruses.. Genome Biol Evol 2015 Oct 21;7(11):2996-3008.
Kapoor A, Simmonds P, Gerold G, Qaisar N, Jain K, Henriquez JA, Firth C, Hirschberg DL, Rice CM, Shields S, Lipkin WI. Characterization of a canine homolog of hepatitis C virus.. Proc Natl Acad Sci U S A 2011 Jul 12;108(28):11608-13.
Orlando L, Ginolhac A, Zhang G, Froese D, Albrechtsen A, Stiller M, Schubert M, Cappellini E, Petersen B, Moltke I, Johnson PL, Fumagalli M, Vilstrup JT, Raghavan M, Korneliussen T, Malaspinas AS, Vogt J, Szklarczyk D, Kelstrup CD, Vinther J, Dolocan A, Stenderup J, Velazquez AM, Cahill J, Rasmussen M, Wang X, Min J, Zazula GD, Seguin-Orlando A, Mortensen C, Magnussen K, Thompson JF, Weinstock J, Gregersen K, Røed KH, Eisenmann V, Rubin CJ, Miller DC, Antczak DF, Bertelsen MF, Brunak S, Al-Rasheid KA, Ryder O, Andersson L, Mundy J, Krogh A, Gilbert MT, Kjær K, Sicheritz-Ponten T, Jensen LJ, Olsen JV, Hofreiter M, Nielsen R, Shapiro B, Wang J, Willerslev E. Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse.. Nature 2013 Jul 4;499(7456):74-8.
Pfaender S, Cavalleri JM, Walter S, Doerrbecker J, Campana B, Brown RJ, Burbelo PD, Postel A, Hahn K, Anggakusuma, Riebesehl N, Baumgärtner W, Becher P, Heim MH, Pietschmann T, Feige K, Steinmann E. Clinical course of infection and viral tissue tropism of hepatitis C virus-like nonprimate hepaciviruses in horses.. Hepatology 2015 Feb;61(2):447-59.
Drexler JF, Kupfer B, Petersen N, Grotto RM, Rodrigues SM, Grywna K, Panning M, Annan A, Silva GF, Douglas J, Koay ES, Smuts H, Netto EM, Simmonds P, Pardini MI, Roth WK, Drosten C. A novel diagnostic target in the hepatitis C virus genome.. PLoS Med 2009 Feb 10;6(2):e31.
Tanaka T, Kasai H, Yamashita A, Okuyama-Dobashi K, Yasumoto J, Maekawa S, Enomoto N, Okamoto T, Matsuura Y, Morimatsu M, Manabe N, Ochiai K, Yamashita K, Moriishi K. Hallmarks of hepatitis C virus in equine hepacivirus.. J Virol 2014 Nov;88(22):13352-66.
Burden FA, Hazell-Smith E, Mulugeta G, Patrick V, Trawford R, Brooks-Brownlie HW. Reference intervals for biochemical and haematological parameters in mature domestic donkeys (Equus asinus) in the UK. Equine Vet Educ 28:134–139.
Gray RR, Parker J, Lemey P, Salemi M, Katzourakis A, Pybus OG. The mode and tempo of hepatitis C virus evolution within and among hosts.. BMC Evol Biol 2011 May 19;11:131.
Pfafferott K, Gaudieri S, Ulsenheimer A, James I, Heeg M, Nolan D, John M, Rauch A, Mallal S, Lucas A, Klenerman P, Diepolder HM, Lucas M. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.. PLoS One 2011 Feb 8;6(2):e16797.
Simmonds P, Tuplin A, Evans DJ. Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence.. RNA 2004 Sep;10(9):1337-51.
Turner SS, Gianella S, Yip MJ, van Seggelen WO, Gillies RD, Foster AL, Barbati ZR, Smith DM, Fierer DS. Shedding of Hepatitis C Virus in Semen of Human Immunodeficiency Virus-Infected Men.. Open Forum Infect Dis 2016 Mar;3(2):ofw057.
Rossel S, Marshall F, Peters J, Pilgram T, Adams MD, O'Connor D. Domestication of the donkey: timing, processes, and indicators.. Proc Natl Acad Sci U S A 2008 Mar 11;105(10):3715-20.
Beja-Pereira A, England PR, Ferrand N, Jordan S, Bakhiet AO, Abdalla MA, Mashkour M, Jordana J, Taberlet P, Luikart G. African origins of the domestic donkey.. Science 2004 Jun 18;304(5678):1781.
Kimura B, Marshall FB, Chen S, Rosenbom S, Moehlman PD, Tuross N, Sabin RC, Peters J, Barich B, Yohannes H, Kebede F, Teclai R, Beja-Pereira A, Mulligan CJ. Ancient DNA from Nubian and Somali wild ass provides insights into donkey ancestry and domestication.. Proc Biol Sci 2011 Jan 7;278(1702):50-7.
Pfaender S, Walter S, Todt D, Behrendt P, Doerrbecker J, Wölk B, Engelmann M, Gravemann U, Seltsam A, Steinmann J, Burbelo PD, Klawonn F, Feige K, Pietschmann T, Cavalleri JV, Steinmann E. Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure.. J Gen Virol 2015 Sep;96(9):2636-2642.
Levi JE, Cabral SP, Nishiya A, Ferreira S, Romano CM, Polite MB, Pereira RA, Mota MA, Kutner JM. Absence of nonprimate hepacivirus-related genomes in blood donors seroreactive for hepatitis C virus displaying indeterminate blot patterns.. J Viral Hepat 2014 Nov;21(11):e164-6.
Baechlein C, Fischer N, Grundhoff A, Alawi M, Indenbirken D, Postel A, Baron AL, Offinger J, Becker K, Beineke A, Rehage J, Becher P. Identification of a Novel Hepacivirus in Domestic Cattle from Germany.. J Virol 2015 Jul;89(14):7007-15.
Gray RR, Tanaka Y, Takebe Y, Magiorkinis G, Buskell Z, Seeff L, Alter HJ, Pybus OG. Evolutionary analysis of hepatitis C virus gene sequences from 1953.. Philos Trans R Soc Lond B Biol Sci 2013 Sep 19;368(1626):20130168.
Huang J, Zhao Y, Bai D, Shiraigol W, Li B, Yang L, Wu J, Bao W, Ren X, Jin B, Zhao Q, Li A, Bao S, Bao W, Xing Z, An A, Gao Y, Wei R, Bao Y, Bao T, Han H, Bai H, Bao Y, Zhang Y, Daidiikhuu D, Zhao W, Liu S, Ding J, Ye W, Ding F, Sun Z, Shi Y, Zhang Y, Meng H, Dugarjaviin M. Donkey genome and insight into the imprinting of fast karyotype evolution.. Sci Rep 2015 Sep 16;5:14106.
Alcaide M, Rico C, Ruiz S, Soriguer R, Muñoz J, Figuerola J. Disentangling vector-borne transmission networks: a universal DNA barcoding method to identify vertebrate hosts from arthropod bloodmeals.. PLoS One 2009 Sep 21;4(9):e7092.
Lemey P, Kosakovsky Pond SL, Drummond AJ, Pybus OG, Shapiro B, Barroso H, Taveira N, Rambaut A. Synonymous substitution rates predict HIV disease progression as a result of underlying replication dynamics.. PLoS Comput Biol 2007 Feb 16;3(2):e29.
Murrell B, Weaver S, Smith MD, Wertheim JO, Murrell S, Aylward A, Eren K, Pollner T, Martin DP, Smith DM, Scheffler K, Kosakovsky Pond SL. Gene-wide identification of episodic selection.. Mol Biol Evol 2015 May;32(5):1365-71.
Rambaut A, Lam TT, Max Carvalho L, Pybus OG. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen).. Virus Evol 2016 Jan;2(1):vew007.
Li YQ, Ghafari M, Holbrook AJ, Boonen I, Amor N, Catalano S, Webster JP, Li YY, Li HT, Vergote V, Maes P, Chong YL, Laudisoit A, Baelo P, Ngoy S, Mbalitini SG, Gembu GC, Akawa PM, Goüy de Bellocq J, Leirs H, Verheyen E, Pybus OG, Katzourakis A, Alagaili AN, Gryseels S, Li YC, Suchard MA, Bletsa M, Lemey P. The evolutionary history of hepaciviruses. bioRxiv 2023 Jun 30;.
Yuan S, Yao XY, Lian CY, Kong S, Shao JW, Zhang XL. Molecular detection and genetic characterization of bovine hepacivirus identified in ticks collected from cattle in Harbin, northeastern China. Front Vet Sci 2023;10:1093898.
Khan MZI, Nazli A, Al-Furas H, Asad MI, Ajmal I, Khan D, Shah J, Farooq MA, Jiang W. An overview of viral mutagenesis and the impact on pathogenesis of SARS-CoV-2 variants. Front Immunol 2022;13:1034444.
Jiang J, Hao Y, He B, Su L, Li X, Liu X, Chen C, Chen L, Zhao Z, Mi S, Deng X, Gong W, Tu C. Severe Acute Hepatitis Outbreaks Associated with a Novel Hepacivirus in Rhizomys pruinosus in Hainan, China. J Virol 2022 Sep 14;96(17):e0078222.
Hufsky F, Abecasis A, Agudelo-Romero P, Bletsa M, Brown K, Claus C, Deinhardt-Emmer S, Deng L, Friedel CC, Gismondi MI, Kostaki EG, Kühnert D, Kulkarni-Kale U, Metzner KJ, Meyer IM, Miozzi L, Nishimura L, Paraskevopoulou S, Pérez-Cataluña A, Rahlff J, Thomson E, Tumescheit C, van der Hoek L, Van Espen L, Vandamme AM, Zaheri M, Zuckerman N, Marz M. Women in the European Virus Bioinformatics Center. Viruses 2022 Jul 12;14(7).
Breitfeld J, Fischer N, Tsachev I, Marutsov P, Baymakova M, Plhal R, Keuling O, Becher P, Baechlein C. Expanded Diversity and Host Range of Bovine Hepacivirus-Genomic and Serological Evidence in Domestic and Wild Ruminant Species. Viruses 2022 Jun 30;14(7).
Zhang XL, Yao XY, Zhang YQ, Lv ZH, Liu H, Sun J, Shao JW. A Highly Divergent Hepacivirus Identified in Domestic Ducks Further Reveals the Genetic Diversity of Hepaciviruses. Viruses 2022 Feb 11;14(2).
Shao JW, Guo LY, Yuan YX, Ma J, Chen JM, Liu Q. A Novel Subtype of Bovine Hepacivirus Identified in Ticks Reveals the Genetic Diversity and Evolution of Bovine Hepacivirus. Viruses 2021 Nov 2;13(11).
Bletsa M, Vrancken B, Gryseels S, Boonen I, Fikatas A, Li Y, Laudisoit A, Lequime S, Bryja J, Makundi R, Meheretu Y, Akaibe BD, Mbalitini SG, Van de Perre F, Van Houtte N, Těšíková J, Wollants E, Van Ranst M, Pybus OG, Drexler JF, Verheyen E, Leirs H, Gouy de Bellocq J, Lemey P. Molecular detection and genomic characterization of diverse hepaciviruses in African rodents. Virus Evol 2021 Jan;7(1):veab036.
Rasche A, Lehmann F, Goldmann N, Nagel M, Moreira-Soto A, Nobach D, de Oliveira Carneiro I, Osterrieder N, Greenwood AD, Steinmann E, Lukashev AN, Schuler G, Glebe D, Drexler JF. A hepatitis B virus causes chronic infections in equids worldwide. Proc Natl Acad Sci U S A 2021 Mar 30;118(13).
Moreira-Soto A, Arroyo-Murillo F, Sander AL, Rasche A, Corman V, Tegtmeyer B, Steinmann E, Corrales-Aguilar E, Wieseke N, Avey-Arroyo J, Drexler JF. Cross-order host switches of hepatitis C-related viruses illustrated by a novel hepacivirus from sloths. Virus Evol 2020 Jul;6(2):veaa033.
Tomlinson JE, Kapoor A, Kumar A, Tennant BC, Laverack MA, Beard L, Delph K, Davis E, Schott Ii H, Lascola K, Holbrook TC, Johnson P, Taylor SD, McKenzie E, Carter-Arnold J, Setlakwe E, Fultz L, Brakenhoff J, Ruby R, Trivedi S, Van de Walle GR, Renshaw RW, Dubovi EJ, Divers TJ. Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014-2018). J Vet Intern Med 2019 Jan;33(1):251-257.
Hake N, von Holtum C, Höper D, Nijhof AM, Dietze K, Hoffmann B. Identification and Long-Term Detection of Hepacivirus bovis Genotype 1 and 2 on a Cattle Farm in Germany. Viruses 2026 Jan 6;18(1).
Săndulescu O, Matičič M, Garcia F, Blomé MA, Mondelli MU, Irving W, Zidovec-Lepej S, Widell A, Şahin GÖ. Evolving insights into viral hepatitis: Advances, evidence, and expert perspectives from the ESCMID Study Group for Viral Hepatitis (ESGVH) - Part 2: hepatitis B, C, and delta. Germs 2025 Sep;15(3):263-273.
Tanaka T, Akaike Y, Kasai H, Yamashita A, Matsuura Y, Moriishi K. Identification of claudin-3 as an entry factor for rat hepacivirus. Proc Natl Acad Sci U S A 2025 Oct 7;122(40):e2508736122.
Xu W, Wang W, Sui L, Liu N, Zhao Y, Liu Q. A novel genotype of Hepacivirus bovis identified in reindeer (Rangifer tarandus) in northeastern China. Front Cell Infect Microbiol 2025;15:1646191.
Cardone R, Buonavoglia A, Lanave G, Vasinioti VI, Mininni V, Lorusso E, Decaro N, Martella V, Elia G, Diakoudi G. Description of an Equine Hepacivirus Cluster in a Horse Stable in Italy. Transbound Emerg Dis 2023;2023:5251034.