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Archives of Virology

, Volume 164, Issue 2, pp 391–400 | Cite as

Molecular identification and characterization of nonprimate hepaciviruses in equines

  • Kore Schlottau
  • Sasan Fereidouni
  • Martin Beer
  • Bernd HoffmannEmail author
Original Article

Abstract

Hepatitis C virus (HCV) is a positive-sense RNA virus belonging to the genus Hepacivirus, family Flaviviridae. Its genome has a length of 9.6 kb and encodes a single polyprotein flanked by two untranslated regions. HCV can cause liver cirrhosis and hepatocellular carcinoma, and approximately 2% of the world’s population is chronically infected. The investigation of pathogenesis is complicated due to the lack of an animal model. The origin of this virus remains unclear, but in the last few years, relatives of HCV were initially identified in dogs and later in horses, rodents, bats and Old World monkeys. Non-primate hepacivirus (NPHV), which infects dogs and horses, is the closest relative to HCV. We established a pan-reactive “panHepaci”-RT-qPCR assay, which is able to detect human HCV as well as equine NPHV, and additionally, an equine-specific “equHepaci”-RT-qPCR for confirmation of positive results. Serum samples from 1158 clinically inconspicuous horses from Germany and several samples from other mammalian species were screened. We found 2.4% of the horses positive for hepacivirus RNA, and furthermore, the “panHepaci”-RT-qPCR assay also detected a hepacivirus in a donkey from Egypt. This virus had only 78% sequence identity in the E2 gene when compared to other known NPHVs. The established method could be useful for screening purposes, since it is likely that related hepaciviruses also occur in other species.

Notes

Acknowledgements

We thank Susanne Zahnow, Patrick Zitzow, Doreen Lange and Christian Korthase at the Friedrich-Loeffler-Institute for excellent technical assistance. We also thank Dr. Ahmed S. Abdel-Moneim, Dr. Shawky M. Aboelhadid and Dr. Ahmad E. Abdel-Ghany from Beni Suef University, Egypt, as well as Prof. Dr. Klaus Osterrieder from Freie Universität Berlin, Germany, for providing serum samples. We thank Marhild Kortenbusch and Dr. Annemarie Berger from the Universitätsklinikum Frankfurt, Institute of Medical Virology, for providing the hepatitis C virus RNA.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

705_2018_4077_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 20 kb)

References

  1. 1.
    Baechlein C, Fischer N, Grundhoff A, Alawi M, Indenbirken D, Postel A, Baron AL, Offinger J, Becker K, Beineke A, Rehage J, Becher P (2015) Identification of a novel hepacivirus in domestic cattle from Germany. J Virol 89:7007–7015CrossRefGoogle Scholar
  2. 2.
    Bexfield NH, Watson PJ, Heaney J, Heeney JL, Tiley L (2014) Canine hepacivirus is not associated with chronic liver disease in dogs. J Viral Hepat 21:223–228CrossRefGoogle Scholar
  3. 3.
    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 86:6171–6178CrossRefGoogle Scholar
  4. 4.
    Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362CrossRefGoogle Scholar
  5. 5.
    Corman VM, Grundhoff A, Baechlein C, Fischer N, Gmyl A, Wollny R, Dei D, Ritz D, Binger T, Adankwah E, Marfo KS, Annison L, Annan A, Adu-Sarkodie Y, Oppong S, Becher P, Drosten C, Drexler JF (2015) Highly divergent hepaciviruses from African cattle. J Virol 89:5876–5882CrossRefGoogle Scholar
  6. 6.
    Drexler JF, Corman VM, Muller 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, Kummerer BM, Kruger DH, Schmidt-Chanasit J, Setien 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:e1003438CrossRefGoogle Scholar
  7. 7.
    El-Attar LM, Mitchell JA, Brooks Brownlie H, Priestnall SL, Brownlie J (2015) Detection of non-primate hepaciviruses in UK dogs. Virology 484:93–102CrossRefGoogle Scholar
  8. 8.
    Elia G, Lanave G, Lorusso E, Parisi A, Cavaliere N, Patruno G, Terregino C, Decaro N, Martella V, Buonavoglia C (2017) Identification and genetic characterization of equine hepaciviruses in Italy. Vet Microbiol 207:239–247CrossRefGoogle Scholar
  9. 9.
    Elia G, Lanave G, Lorusso E, Parisi A, Trotta A, Buono R, Martella V, Decaro N, Buonavoglia C (2017) Equine hepacivirus persistent infection in a horse with chronic wasting. Transbound Emerg Dis 64:1354–1358CrossRefGoogle Scholar
  10. 10.
    Fereidouni SR, Harder TC, Gaidet N, Ziller M, Hoffmann B, Hammoumi S, Globig A, Starick E (2012) Saving resources: avian influenza surveillance using pooled swab samples and reduced reaction volumes in real-time RT-PCR. J Virol Methods 186:119–125CrossRefGoogle Scholar
  11. 11.
    Figueiredo AS, Lampe E, do Espirito-Santo MP, Mello FC, de Almeida FQ, de Lemos ER, Godoi TL, Dimache LA, Dos Santos DR, Villar LM (2015) Identification of two phylogenetic lineages of equine hepacivirus and high prevalence in Brazil. Vet J 206:414–416CrossRefGoogle Scholar
  12. 12.
    Firth C, Bhat M, Firth MA, Williams SH, Frye MJ, Simmonds P, Conte JM, Ng J, Garcia J, Bhuva NP, Lee B, Che X, Quan PL, Lipkin WI (2014) Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus in New York City. mBio 5:e01933-01914CrossRefGoogle Scholar
  13. 13.
    Gather T, Walter S, Pfaender S, Todt D, Feige K, Steinmann E, Cavalleri JM (2016) Acute and chronic infections with nonprimate hepacivirus in young horses. Vet Res 47:97CrossRefGoogle Scholar
  14. 14.
    Gemaque BS, Souza Junior, de Souza A, do Carmo Pereira Soares M, Malheiros AP, Silva AL, Alves MM, Gomes-Gouvea MS, Pinho JR, Ferreira de Figueiredo H, Ribeiro DB, Souza da Silva J, Moraes LA, Ribeiro AS, Pereira WL (2014) Hepacivirus infection in domestic horses, Brazil, 2011-2013. Emerg Infect Dis 20:2180–2182CrossRefGoogle Scholar
  15. 15.
    Guindon S, Gascuel O (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52:696–704CrossRefGoogle Scholar
  16. 16.
    Hayashi S, Tanaka T, Moriishi K, Hirayama K, Yamada A, Hotta K (2018) Seroepidemiology of non-primate hepacivirus (NPHV) in Japanese native horses. J Vet Med Sci/Jpn Soc Vet Sci 80:186–189CrossRefGoogle Scholar
  17. 17.
    Hoffmann B, Depner K, Schirrmeier H, Beer M (2006) A universal heterologous internal control system for duplex real-time RT-PCR assays used in a detection system for pestiviruses. J Virol Methods 136:200–209CrossRefGoogle Scholar
  18. 18.
    Hoffmann B, Tappe D, Höper D, Herden C, Boldt A, Mawrin C, Niederstrasser O, Muller T, Jenckel M, van der Grinten E, Lutter C, Abendroth B, Teifke JP, Cadar D, Schmidt-Chanasit J, Ulrich RG, Beer M (2015) A variegated squirrel bornavirus associated with fatal human encephalitis. N Engl J Med 373:154–162CrossRefGoogle Scholar
  19. 19.
    Hoofnagle JH (1997) Hepatitis C virus the clinical spectrum. Hepatology 26:15–20CrossRefGoogle Scholar
  20. 20.
    Kapoor A, Simmonds P, Gerold G, Qaisar N, Jain K, Henriquez JA, Firth C, Hirschberg DL, Rice CM, Shields S, Lipkin WI (2011) Characterization of a canine homolog of hepatitis C virus. Proc Natl Acad Sci USA 108:11608–11613CrossRefGoogle Scholar
  21. 21.
    Kapoor A, Simmonds P, Scheel TK, Hjelle B, Cullen JM, Burbelo PD, Chauhan LV, Duraisamy R, Sanchez Leon M, Jain K, Vandegrift KJ, Calisher CH, Rice CM, Lipkin WI (2013) Identification of rodent homologs of hepatitis C virus and pegiviruses. mBio 4:e00216-00213CrossRefGoogle Scholar
  22. 22.
    Katoh K, Misawa K, Kuma K-I, Miyata T (2002) MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30:3059–3066CrossRefGoogle Scholar
  23. 23.
    Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, Buxton S, Cooper A, Markowitz S, Duran C, Thierer T, Ashton B, Meintjes P, Drummond A (2012) Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28:1647–1649CrossRefGoogle Scholar
  24. 24.
    Kim HS, Moon HW, Sung HW, Kwon HM (2017) First identification and phylogenetic analysis of equine hepacivirus in Korea. Infect Genet Evol 49:268–272CrossRefGoogle Scholar
  25. 25.
    Kolykhalov AA, Agapov EV, Blight KJ, Mihalik K, Feinstone SM, Rice CM (1997) Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277:570–574CrossRefGoogle Scholar
  26. 26.
    Lauck M, Sibley SD, Lara J, Purdy MA, Khudyakov Y, Hyeroba D, Tumukunde A, Weny G, Switzer WM, Chapman CA, Hughes AL, Friedrich TC, O’Connor DH, Goldberg TL (2013) A novel hepacivirus with an unusually long and intrinsically disordered NS5A protein in a wild Old World primate. J Virol 87:8971–8981CrossRefGoogle Scholar
  27. 27.
    Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM (2005) Complete replication of hepatitis C virus in cell culture. Science 309:623–626CrossRefGoogle Scholar
  28. 28.
    Lu G, Sun L, Xu T, He D, Wang Z, Ou S, Jia K, Yuan L, Li S (2016) First description of hepacivirus and pegivirus infection in domestic horses in China: a study in Guangdong Province, Heilongjiang Province and Hong Kong District. PLoS One 11:e0155662CrossRefGoogle Scholar
  29. 29.
    Lyons S, Kapoor A, Sharp C, Schneider BS, Wolfe ND, Culshaw G, Corcoran B, McGorum BC, Simmonds P (2012) Nonprimate hepaciviruses in domestic horses, United Kingdom. Emerg Infect Dis 18:1976–1982CrossRefGoogle Scholar
  30. 30.
    Lyons S, Kapoor A, Schneider BS, Wolfe ND, Culshaw G, Corcoran B, Durham AE, Burden F, McGorum BC, Simmonds P (2014) Viraemic frequencies and seroprevalence of non-primate hepacivirus and equine pegiviruses in horses and other mammalian species. J Gen Virol 95:1701–1711CrossRefGoogle Scholar
  31. 31.
    Makuwa M, Souquiere S, Telfer P, Bourry O, Rouquet P, Kazanji M, Roques P, Simon F (2006) Hepatitis viruses in non-human primates. J Med Primatol 35:384–387CrossRefGoogle Scholar
  32. 32.
    Matsuu A, Hobo S, Ando K, Sanekata T, Sato F, Endo Y, Amaya T, Osaki T, Horie M, Masatani T, Ozawa M, Tsukiyama-Kohara K (2015) Genetic and serological surveillance for non-primate hepacivirus in horses in Japan. Vet Microbiol 179:219–227CrossRefGoogle Scholar
  33. 33.
    Moradpour D, Penin F, Rice CM (2007) Replication of hepatitis C virus. Nat Rev Microbiol 5:453–463CrossRefGoogle Scholar
  34. 34.
    Pfaender S, Brown RJP, Pietschmann T, Steinmann E (2014) Natural reservoirs for homologs of hepatitis C virus. Emerg Microbes Infect 3:e21CrossRefGoogle Scholar
  35. 35.
    Pfaender S, Cavalleri JM, Walter S, Doerrbecker J, Campana B, Brown RJ, Burbelo PD, Postel A, Hahn K, Anggakusuma Riebesehl N, Baumgartner W, Becher P, Heim MH, Pietschmann T, Feige K, Steinmann E (2015) Clinical course of infection and viral tissue tropism of hepatitis C virus-like nonprimate hepaciviruses in horses. Hepatology 61:447–459CrossRefGoogle Scholar
  36. 36.
    Pfaender S, Walter S, Todt D, Behrendt P, Doerrbecker J, Wolk B, Engelmann M, Gravemann U, Seltsam A, Steinmann J, Burbelo PD, Klawonn F, Feige K, Pietschmann T, Cavalleri JM, Steinmann E (2015) 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 96:2636–2642CrossRefGoogle Scholar
  37. 37.
    Pfaender S, Walter S, Grabski E, Todt D, Bruening J, Romero-Brey I, Gather T, Brown RJ, Hahn K, Puff C, Pfankuche VM, Hansmann F, Postel A, Becher P, Thiel V, Kalinke U, Wagner B, Bartenschlager R, Baumgartner W, Feige K, Pietschmann T, Cavalleri JM, Steinmann E (2017) Immune protection against reinfection with nonprimate hepacivirus. Proc Nat Acad Sci USA 114:E2430–E2439CrossRefGoogle Scholar
  38. 38.
    Polaris Observatory HCVC (2017) Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2:161–176CrossRefGoogle Scholar
  39. 39.
    Pronost S, Hue E, Fortier C, Foursin M, Fortier G, Desbrosse F, Rey FA, Pitel PH, Richard E, Saunier B (2017) Prevalence of equine hepacivirus infections in France and evidence for two viral subtypes circulating worldwide. Transboundary Emerg Dis 64:1884–1897CrossRefGoogle Scholar
  40. 40.
    Puchades Renau L, Berenguer M (2018) Introduction to hepatitis C virus infection: overview and history of hepatitis C virus therapies. Hemodial Int 22(Suppl 1):S8–S21CrossRefGoogle Scholar
  41. 41.
    Pybus OG, Theze J (2016) Hepacivirus cross-species transmission and the origins of the hepatitis C virus. Curr Opin Virol 16:1–7CrossRefGoogle Scholar
  42. 42.
    Quan PL, Firth C, Conte JM, Williams SH, Zambrana-Torrelio CM, Anthony SJ, Ellison JA, Gilbert AT, Kuzmin I, Niezgoda M, Osinubi MOV, Recuenco S, Markotter W, Breiman RF, Kalemba L, Malekani J, Lindblade KA, Rostal MK, Ojeda-Flores R, Suzan G, Davis LB, Blau DM, Ogunkoya AB, Alvarez Castillo DA, Moran D, Ngam S, Akaibe D, Agwanda B, Briese T, Epstein JH, Daszak P, Rupprecht CE, Holmes EC, Lipkin WI (2014) Bats are a major natural reservoir for hepaciviruses and pegiviruses. PNAS 110:8194–8199CrossRefGoogle Scholar
  43. 43.
    Ramsay JD, Evanoff R, Wilkinson TE Jr, Divers TJ, Knowles DP, Mealey RH (2015) Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus. Hepatology 61:1533–1546CrossRefGoogle Scholar
  44. 44.
    Reichert C, Campe A, Walter S, Pfaender S, Welsch K, Ruddat I, Sieme H, Feige K, Steinmann E, Cavalleri JMV (2017) Frequent occurrence of nonprimate hepacivirus infections in thoroughbred breeding horses—a cross-sectional study for the occurrence of infections and potential risk factors. Vet Microbiol 203:315–322CrossRefGoogle Scholar
  45. 45.
    Reuter G, Maza N, Pankovics P, Boros A (2014) Non-primate hepacivirus infection with apparent hepatitis in a horse—short communication. Acta Vet Hung 62:422–427CrossRefGoogle Scholar
  46. 46.
    Scheel TK, Simmonds P, Kapoor A (2015) Surveying the global virome: identification and characterization of HCV-related animal hepaciviruses. Antiviral Res 115:83–93CrossRefGoogle Scholar
  47. 47.
    Scheel TK, Kapoor A, Nishiuchi E, Brock KV, Yu Y, Andrus L, Gu M, Renshaw RW, Dubovi EJ, McDonough SP, Van de Walle GR, Lipkin WI, Divers TJ, Tennant BC, Rice CM (2015) Characterization of nonprimate hepacivirus and construction of a functional molecular clone. Proc Natl Acad Sci USA 112:2192–2197CrossRefGoogle Scholar
  48. 48.
    Scheel TK, Simmonds P, Kapoor A (2015) Surveying the global virome: identification and characterization of HCV-related animal hepaciviruses. Antivir Res 115:83–93CrossRefGoogle Scholar
  49. 49.
    Shi M, Lin XD, Vasilakis N, Tian JH, Li CX, Chen LJ, Eastwood G, Diao XN, Chen MH, Chen X, Qin XC, Widen SG, Wood TG, Tesh RB, Xu J, Holmes EC, Zhang YZ (2015) Divergent viruses discovered in arthropods and vertebrates revise the evolutionary history of the flaviviridae and related viruses. J Virol 90:659–669CrossRefGoogle Scholar
  50. 50.
    Simmonds P (2004) Genetic diversity and evolution of hepatitis C virus—15 years on. J Gen Virol 85:3173–3188CrossRefGoogle Scholar
  51. 51.
    Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P (2014) Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology 59:318–327CrossRefGoogle Scholar
  52. 52.
    Smith DB, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff AS, Pletnev A, Rico-Hesse R, Stapleton JT, Simmonds P (2016) Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family. J Gen Virol 97:2894–2907CrossRefGoogle Scholar
  53. 53.
    Stapleton JT, Foung S, Muerhoff AS, Bukh J, Simmonds P (2011) The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae. J Gen Virol 92:233–246CrossRefGoogle Scholar
  54. 54.
    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 (2014) Hallmarks of hepatitis C virus in equine hepacivirus. J Virol 88:13352–13366CrossRefGoogle Scholar
  55. 55.
    Toussaint JF, Sailleau C, Breard E, Zientara S, De Clercq K (2007) Bluetongue virus detection by two real-time RT-qPCRs targeting two different genomic segments. J Virol Methods 140:115–123CrossRefGoogle Scholar
  56. 56.
    van der Laan LJ, de Ruiter PE, van Gils IM, Fieten H, Spee B, Pan Q, Rothuizen J, Penning LC (2014) Canine hepacivirus and idiopathic hepatitis in dogs from a Dutch cohort. J Viral Hepat 21:894–896CrossRefGoogle Scholar
  57. 57.
    Walter S, Rasche A, Moreira-Soto A, Pfaender S, Bletsa M, Corman VM, Aguilar-Setien A, Garcia-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, Garcia-Bocanegra I, Jores J, Carluccio A, Veronesi MC, Cavalleri JM, Drosten C, Lemey P, Steinmann E, Drexler JF (2017) Differential infection patterns and recent evolutionary origins of equine hepaciviruses in donkeys. J Virol 91(1):e01711-16CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Diagnostic Virology, Friedrich-Loeffler-InstitutGreifswald-Insel RiemsGermany
  2. 2.University of ViennaWienAustria

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