FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Proc Natl Acad Sci U S A / Immune protection against reinfection with nonprimate hepaci...
Proceedings of the National Academy of Sciences of the United States of America2017; 114(12); E2430-E2439; doi: 10.1073/pnas.1619380114

Immune protection against reinfection with nonprimate hepacivirus.

Abstract: Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV), which shares similar features with HCV and thus represents an animal model to study hepacivirus infections in their natural hosts. We aimed to dissect equine immune responses after experimental NPHV infection and conducted challenge experiments to investigate immune protection against secondary NPHV infections. Horses were i.v. injected with NPHV containing plasma. Flow cytometric analysis was used to monitor immune cell frequencies and activation status. All infected horses became viremic after 1 or 2 wk and viremia could be detected in two horses for several weeks followed by a delayed seroconversion and viral clearance. Histopathological examinations of liver biopsies revealed mild, periportally accentuated infiltrations of lymphocytes, macrophages, and plasma cells with some horses displaying subclinical signs of hepatitis. Following viral challenge, an activation of equine immune responses was observed. Importantly, after a primary NPHV infection, horses were protected against rechallenge with the homologous as well as a distinct isolate with only minute amounts of circulating virus being detectable.
Get Full Text
Publication Date: 2017-03-08 PubMed ID: 28275093PubMed Central: PMC5373355DOI: 10.1073/pnas.1619380114Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates how horses’ immune systems respond to and protect against subsequent infections of nonprimate hepacivirus (NPHV), a virus very similar to human Hepatitis C Virus (HCV). Through experimental infection and subsequent re-infection, results showed the horses’ immune systems were activated and effective in defending against the virus.

Article Explanation and Detailed Discussion

  • The Hepatitis C virus (HCV), which is restricted in infecting only humans and chimpanzees, has a close homolog in the nonprimate hepacivirus (NPHV) found in horses. This similarity offers an opportunity to study hepacivirus infections within their natural hosts (horses), which can reveal information about how the same might happen in humans.
  • The study aimed to understand the equine (horse) immune responses to NPHV by initiating an experimental NPHV infection in the horses, and later reexposing them to the virus. The goal was to evaluate whether these horses, once exposed to the virus, could build immunity and protect themselves against subsequent infections.
  • Flow cytometric analysis, a technique used to measure physical and chemical characteristics of cells, was used to monitor changes in immune cell frequencies and activation status.
  • All the horses that were intravenously injected with NPHV containing plasma turned out to be viremic (presence of virus in the bloodstream) after 1 or 2 weeks. However, viremia continued to be detected in a couple of horses for several weeks which was followed by a delayed seroconversion, the period during which a specific antibody develops and becomes detectable in the blood, and subsequent viral clearance.
  • Liver biopsies showed mild infiltrations of lymphocytes (white blood cells that play a key role in immune response), macrophages (a type of white blood cell that consumes foreign substances), and plasma cells (cells that produce antibodies). Some horses displayed subclinical signs of hepatitis – mild and not severe symptoms.
  • Crucially, after the initial NPHV infection, when rechallenged with the same virus, the horses were protected. Notably, this immunity extended to a different strain of the virus, with only small amounts of circulating virus detectable.

This study contributes to understanding HCV by studying its homolog in horses, NPHV. The immune response observed in horses could be indicative of the potential human immune response, offering insights into virus control, pathogenesis, and possible vaccination strategies.

Cite This Article

APA
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, Baumgärtner W, Feige K, Pietschmann T, Cavalleri JM, Steinmann E. (2017). Immune protection against reinfection with nonprimate hepacivirus. Proc Natl Acad Sci U S A, 114(12), E2430-E2439. https://doi.org/10.1073/pnas.1619380114

Publication

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 114
Issue: 12
Pages: E2430-E2439

Researcher Affiliations

Pfaender, Stephanie
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
  • Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
  • Federal Department of Home Affairs, Institute of Virology and Immunology, 3012 Bern and 3147 Mittelhäusern, Switzerland.
Walter, Stephanie
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
Grabski, Elena
  • Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
Todt, Daniel
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
Bruening, Janina
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
Romero-Brey, Inés
  • Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
Gather, Theresa
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Brown, Richard J P
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
Hahn, Kerstin
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Puff, Christina
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Pfankuche, Vanessa M
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Hansmann, Florian
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Postel, Alexander
  • Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Becher, Paul
  • Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Thiel, Volker
  • Department of Infectious Diseases and Pathobiology, University of Bern, 3012 Bern, Switzerland.
  • Federal Department of Home Affairs, Institute of Virology and Immunology, 3012 Bern and 3147 Mittelhäusern, Switzerland.
Kalinke, Ulrich
  • Institute for Experimental Infection Research, Twincore Centre for Experimental and Clinical Infection Research, MHH-HZI, 30625 Hannover, Germany.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Bartenschlager, Ralf
  • Department of Infectious Diseases, Molecular Virology, Heidelberg University, 69120 Heidelberg, Germany.
  • Division of Virus-Associated Carcinogenesis, German Cancer Research Center, 69120 Heidelberg, Germany.
  • German Center for Infection Research, Heidelberg University, 69117 Heidelberg, Germany.
Baumgärtner, Wolfgang
  • Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Pietschmann, Thomas
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany.
Cavalleri, Jessika M V
  • Clinic for Horses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; eike.steinmann@twincore.de jessika.cavalleri@tiho-hannover.de.
Steinmann, Eike
  • Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany; eike.steinmann@twincore.de jessika.cavalleri@tiho-hannover.de.

MeSH Terms

  • Animals
  • Antibodies, Viral / immunology
  • Disease Models, Animal
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C / immunology
  • Hepatitis C / prevention & control
  • Hepatitis C / veterinary
  • Hepatitis C / virology
  • Horse Diseases / immunology
  • Horse Diseases / prevention & control
  • Horse Diseases / virology
  • Horses
  • Humans
  • Phylogeny
  • T-Lymphocytes / immunology

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 52 references
  1. WHO. Hepatitis C: Fact Sheet no. 164. 2016.
  2. Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection.. Nat Rev Gastroenterol Hepatol 2013 Sep;10(9):553-62.
    pubmed: 23817321doi: 10.1038/nrgastro.2013.107google scholar: lookup
  3. Simmonds P. Genetic diversity and evolution of hepatitis C virus--15 years on.. J Gen Virol 2004 Nov;85(Pt 11):3173-3188.
    pubmed: 15483230doi: 10.1099/vir.0.80401-0google scholar: lookup
  4. Martell M, Esteban JI, Quer J, Genescà J, Weiner A, Esteban R, Guardia J, Gómez J. Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution.. J Virol 1992 May;66(5):3225-9.
    pmc: PMC241092pubmed: 1313927doi: 10.1128/jvi.66.5.3225-3229.1992google scholar: lookup
  5. Reddy KR, Lim JK, Kuo A, Di Bisceglie AM, Galati JS, Morelli G, Everson GT, Kwo PY, Brown RS Jr, Sulkowski MS, Akuschevich L, Lok AS, Pockros PJ, Vainorius M, Terrault NA, Nelson DR, Fried MW, Manns MP. All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.. Aliment Pharmacol Ther 2017 Jan;45(1):115-126.
    pubmed: 27790729doi: 10.1111/apt.13823google scholar: lookup
  6. Baumert TF, Fauvelle C, Chen DY, Lauer GM. A prophylactic hepatitis C virus vaccine: a distant peak still worth climbing.. J Hepatol 2014 Nov;61(1 Suppl):S34-44.
    pubmed: 25443345doi: 10.1016/j.jhep.2014.09.009google scholar: lookup
  7. Houghton M, Abrignani S. Prospects for a vaccine against the hepatitis C virus.. Nature 2005 Aug 18;436(7053):961-6.
    pubmed: 16107836doi: 10.1038/nature04081google scholar: lookup
  8. Verstrepen BE, Boonstra A, Koopman G. Immune mechanisms of vaccine induced protection against chronic hepatitis C virus infection in chimpanzees.. World J Hepatol 2015 Jan 27;7(1):53-69.
    pmc: PMC4295194pubmed: 25624997doi: 10.4254/wjh.v7.i1.53google scholar: lookup
  9. Pfaender S, Brown RJ, Pietschmann T, Steinmann E. Natural reservoirs for homologs of hepatitis C virus.. Emerg Microbes Infect 2014 Mar;3(3):e21.
    pmc: PMC3974340pubmed: 26038514doi: 10.1038/emi.2014.19google scholar: lookup
  10. Hartlage AS, Cullen JM, Kapoor A. The Strange, Expanding World of Animal Hepaciviruses.. Annu Rev Virol 2016 Sep 29;3(1):53-75.
    pmc: PMC5523456pubmed: 27741408doi: 10.1146/annurev-virology-100114-055104google scholar: lookup
  11. 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.
    pmc: PMC3136326pubmed: 21610165doi: 10.1073/pnas.1101794108google scholar: lookup
  12. 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. Serology-enabled discovery of genetically diverse hepaciviruses in a new host.. J Virol 2012 Jun;86(11):6171-8.
    pmc: PMC3372197pubmed: 22491452doi: 10.1128/jvi.00250-12google scholar: lookup
  13. 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. Evidence for novel hepaciviruses in rodents.. PLoS Pathog 2013;9(6):e1003438.
    pmc: PMC3688547pubmed: 23818848doi: 10.1371/journal.ppat.1003438google scholar: lookup
  14. 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. Identification of rodent homologs of hepatitis C virus and pegiviruses.. mBio 2013 Apr 9;4(2):e00216-13.
    pmc: PMC3622934pubmed: 23572554doi: 10.1128/mbio.00216-13google scholar: lookup
  15. 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. Detection of zoonotic pathogens and characterization of novel viruses carried by commensal Rattus norvegicus in New York City.. mBio 2014 Oct 14;5(5):e01933-14.
    pmc: PMC4205793pubmed: 25316698doi: 10.1128/mbio.01933-14google scholar: lookup
  16. Quan PL, Firth C, Conte JM, Williams SH, Zambrana-Torrelio CM, Anthony SJ, Ellison JA, Gilbert AT, Kuzmin IV, Niezgoda M, Osinubi MO, 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. Bats are a major natural reservoir for hepaciviruses and pegiviruses.. Proc Natl Acad Sci U S A 2013 May 14;110(20):8194-9.
    pmc: PMC3657805pubmed: 23610427doi: 10.1073/pnas.1303037110google scholar: lookup
  17. 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. A novel hepacivirus with an unusually long and intrinsically disordered NS5A protein in a wild Old World primate.. J Virol 2013 Aug;87(16):8971-81.
    pmc: PMC3754081pubmed: 23740998doi: 10.1128/jvi.00888-13google scholar: lookup
  18. 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.
    pmc: PMC4473572pubmed: 25926652doi: 10.1128/jvi.00534-15google scholar: lookup
  19. 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. Divergent Viruses Discovered in Arthropods and Vertebrates Revise the Evolutionary History of the Flaviviridae and Related Viruses.. J Virol 2016 Jan 15;90(2):659-69.
    pmc: PMC4702705pubmed: 26491167doi: 10.1128/jvi.02036-15google scholar: lookup
  20. 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.
    pubmed: 25212983doi: 10.1002/hep.27440google scholar: lookup
  21. Reuter G, Maza N, Pankovics P, Boros A. Non-primate hepacivirus infection with apparent hepatitis in a horse - Short communication.. Acta Vet Hung 2014 Sep;62(3):422-7.
    pubmed: 25038950doi: 10.1556/avet.2014.011google scholar: lookup
  22. 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. Characterization of nonprimate hepacivirus and construction of a functional molecular clone.. Proc Natl Acad Sci U S A 2015 Feb 17;112(7):2192-7.
    pmc: PMC4343093pubmed: 25646476doi: 10.1073/pnas.1500265112google scholar: lookup
  23. Ramsay JD, Evanoff R, Wilkinson TE Jr, Divers TJ, Knowles DP, Mealey RH. Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus.. Hepatology 2015 May;61(5):1533-46.
    pubmed: 25580897doi: 10.1002/hep.27689google scholar: lookup
  24. Parera M, Martrus G, Franco S, Clotet B, Martinez MA. Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF.. PLoS One 2012;7(8):e42481.
    pmc: PMC3411667pubmed: 22870331doi: 10.1371/journal.pone.0042481google scholar: lookup
  25. Anggakusuma, Brown RJP, Banda DH, Todt D, Vieyres G, Steinmann E, Pietschmann T. Hepacivirus NS3/4A Proteases Interfere with MAVS Signaling in both Their Cognate Animal Hosts and Humans: Implications for Zoonotic Transmission.. J Virol 2016 Dec 1;90(23):10670-10681.
    pmc: PMC5110154pubmed: 27654291doi: 10.1128/jvi.01634-16google scholar: lookup
  26. Egger D, Wölk B, Gosert R, Bianchi L, Blum HE, Moradpour D, Bienz K. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex.. J Virol 2002 Jun;76(12):5974-84.
    pmc: PMC136238pubmed: 12021330doi: 10.1128/jvi.76.12.5974-5984.2002google scholar: lookup
  27. Romero-Brey I, Merz A, Chiramel A, Lee JY, Chlanda P, Haselman U, Santarella-Mellwig R, Habermann A, Hoppe S, Kallis S, Walther P, Antony C, Krijnse-Locker J, Bartenschlager R. Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication.. PLoS Pathog 2012;8(12):e1003056.
    pmc: PMC3516559pubmed: 23236278doi: 10.1371/journal.ppat.1003056google scholar: lookup
  28. Romero-Brey I, Bartenschlager R. Membranous replication factories induced by plus-strand RNA viruses.. Viruses 2014 Jul 22;6(7):2826-57.
    pmc: PMC4113795pubmed: 25054883doi: 10.3390/v6072826google scholar: lookup
  29. Thimme R, Bukh J, Spangenberg HC, Wieland S, Pemberton J, Steiger C, Govindarajan S, Purcell RH, Chisari FV. Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease.. Proc Natl Acad Sci U S A 2002 Nov 26;99(24):15661-8.
    pmc: PMC137773pubmed: 12441397doi: 10.1073/pnas.202608299google scholar: lookup
  30. Bassett SE, Guerra B, Brasky K, Miskovsky E, Houghton M, Klimpel GR, Lanford RE. Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection.. Hepatology 2001 Jun;33(6):1479-87.
    pubmed: 11391537doi: 10.1053/jhep.2001.24371google scholar: lookup
  31. Prince AM, Brotman B, Lee DH, Pfahler W, Tricoche N, Andrus L, Shata MT. Protection against chronic hepatitis C virus infection after rechallenge with homologous, but not heterologous, genotypes in a chimpanzee model.. J Infect Dis 2005 Nov 15;192(10):1701-9.
    pubmed: 16235167doi: 10.1086/496889google scholar: lookup
  32. Grebely J, Prins M, Hellard M, Cox AL, Osburn WO, Lauer G, Page K, Lloyd AR, Dore GJ. Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine.. Lancet Infect Dis 2012 May;12(5):408-14.
    pmc: PMC3608418pubmed: 22541630doi: 10.1016/s1473-3099(12)70010-5google scholar: lookup
  33. Nascimbeni M, Mizukoshi E, Bosmann M, Major ME, Mihalik K, Rice CM, Feinstone SM, Rehermann B. Kinetics of CD4+ and CD8+ memory T-cell responses during hepatitis C virus rechallenge of previously recovered chimpanzees.. J Virol 2003 Apr;77(8):4781-93.
    pmc: PMC152131pubmed: 12663785doi: 10.1128/jvi.77.8.4781-4793.2003google scholar: lookup
  34. Shoukry NH, Grakoui A, Houghton M, Chien DY, Ghrayeb J, Reimann KA, Walker CM. Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection.. J Exp Med 2003 Jun 16;197(12):1645-55.
    pmc: PMC2193956pubmed: 12810686doi: 10.1084/jem.20030239google scholar: lookup
  35. Pfaender S, von Hahn T, Steinmann J, Ciesek S, Steinmann E. Prevention strategies for blood-borne viruses-in the Era of vaccines, direct acting antivirals and antiretroviral therapy.. Rev Med Virol 2016 Sep;26(5):330-9.
    pmc: PMC5084801pubmed: 27185010doi: 10.1002/rmv.1890google scholar: lookup
  36. Bukh J. The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control.. J Hepatol 2016 Oct;65(1 Suppl):S2-S21.
    pubmed: 27641985doi: 10.1016/j.jhep.2016.07.035google scholar: lookup
  37. 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.
    pmc: PMC4249100pubmed: 25210167doi: 10.1128/jvi.02280-14google scholar: lookup
  38. Walter S, Bollenbach A, Doerrbecker J, Pfaender S, Brown RJP, Vieyres G, Scott C, Foster R, Kumar A, Zitzmann N, Griffin S, Penin F, Pietschmann T, Steinmann E. Ion Channel Function and Cross-Species Determinants in Viral Assembly of Nonprimate Hepacivirus p7.. J Virol 2016 May 15;90(10):5075-5089.
    pmc: PMC4859704pubmed: 26962224doi: 10.1128/jvi.00132-16google scholar: lookup
  39. Knolle PA, Thimme R. Hepatic immune regulation and its involvement in viral hepatitis infection.. Gastroenterology 2014 May;146(5):1193-207.
    pubmed: 24412289doi: 10.1053/j.gastro.2013.12.036google scholar: lookup
  40. Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection.. Nature 2005 Aug 18;436(7053):946-52.
    pubmed: 16107834doi: 10.1038/nature04079google scholar: lookup
  41. Midgard H, Weir A, Palmateer N, Lo Re V 3rd, Pineda JA, Macías J, Dalgard O. HCV epidemiology in high-risk groups and the risk of reinfection.. J Hepatol 2016 Oct;65(1 Suppl):S33-S45.
    pubmed: 27641987doi: 10.1016/j.jhep.2016.07.012google scholar: lookup
  42. Lanford RE, Guerra B, Chavez D, Bigger C, Brasky KM, Wang XH, Ray SC, Thomas DL. Cross-genotype immunity to hepatitis C virus.. J Virol 2004 Feb;78(3):1575-81.
    pmc: PMC321392pubmed: 14722311doi: 10.1128/jvi.78.3.1575-1581.2004google scholar: lookup
  43. Lavillette D, Morice Y, Germanidis G, Donot P, Soulier A, Pagkalos E, Sakellariou G, Intrator L, Bartosch B, Pawlotsky JM, Cosset FL. Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection.. J Virol 2005 May;79(10):6023-34.
    pmc: PMC1091689pubmed: 15857988doi: 10.1128/jvi.79.10.6023-6034.2005google scholar: lookup
  44. Logvinoff C, Major ME, Oldach D, Heyward S, Talal A, Balfe P, Feinstone SM, Alter H, Rice CM, McKeating JA. Neutralizing antibody response during acute and chronic hepatitis C virus infection.. Proc Natl Acad Sci U S A 2004 Jul 6;101(27):10149-54.
    pmc: PMC454180pubmed: 15220475doi: 10.1073/pnas.0403519101google scholar: lookup
  45. Postel A, Cavalleri JM, Pfaender S, Walter S, Steinmann E, Fischer N, Feige K, Haas L, Becher P. Frequent presence of hepaci and pegiviruses in commercial equine serum pools.. Vet Microbiol 2016;182:8-14.
    pubmed: 26711022doi: 10.1016/j.vetmic.2015.10.032google scholar: lookup
  46. Lehmbecker A, Liebing J, Barthel Y, Habierski A, Cavalleri J, Puff C, Rademacher B, Lumpe S, Beineke A. Neurolymphomatosis in three horses with multicentric T-cell-rich B-cell lymphoma.. J Comp Pathol 2014 Aug-Oct;151(2-3):181-5.
    pubmed: 24915887doi: 10.1016/j.jcpa.2014.04.004google scholar: lookup
  47. Heinrich F, Jungwirth N, Carlson R, Tipold A, Böer M, Scheibe T, Molnár V, von Dörnberg K, Spitzbarth I, Puff C, Wohlsein P, Baumgärtner W. Immunophenotyping of immune cell populations in the raccoon (Procyon lotor).. Vet Immunol Immunopathol 2015 Dec 15;168(3-4):140-6.
    pubmed: 26672912doi: 10.1016/j.vetimm.2015.10.015google scholar: lookup
  48. Suneetha PV, Schlaphoff V, Wang C, Stegmann KA, Fytili P, Sarin SK, Manns MP, Cornberg M, Wedemeyer H. Effect of peptide pools on effector functions of antigen-specific CD8+ T cells.. J Immunol Methods 2009 Mar 15;342(1-2):33-48.
    pubmed: 19135447doi: 10.1016/j.jim.2008.11.020google scholar: lookup
  49. Schlaphoff V, Lunemann S, Suneetha PV, Jaroszewicz J, Grabowski J, Dietz J, Helfritz F, Bektas H, Sarrazin C, Manns MP, Cornberg M, Wedemeyer H. Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells.. PLoS Pathog 2011 May;7(5):e1002045.
    pmc: PMC3098233pubmed: 21625589doi: 10.1371/journal.ppat.1002045google scholar: lookup
  50. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses.. Vet Immunol Immunopathol 2009 Feb 15;127(3-4):242-8.
    pubmed: 19027964doi: 10.1016/j.vetimm.2008.10.313google scholar: lookup
  51. Gather T, Walter S, Todt D, Pfaender S, Brown RJP, Postel A, Becher P, Moritz A, Hansmann F, Baumgaertner W, Feige K, Steinmann E, Cavalleri JV. Vertical transmission of hepatitis C virus-like non-primate hepacivirus in horses.. J Gen Virol 2016 Oct;97(10):2540-2551.
    pubmed: 27461949doi: 10.1099/jgv.0.000561google scholar: lookup
  52. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.. Mol Biol Evol 2013 Dec;30(12):2725-9.
    pmc: PMC3840312pubmed: 24132122doi: 10.1093/molbev/mst197google scholar: lookup

Citations

This article has been cited 22 times.
  1. Zhang Y, Kinast V, Sheldon J, Frericks N, Todt D, Zimmer M, Caliskan N, Brown RJP, Steinmann E, Pietschmann T. Mouse Liver-Expressed Shiftless Is an Evolutionarily Conserved Antiviral Effector Restricting Human and Murine Hepaciviruses.. Microbiol Spectr 2023 Aug 17;11(4):e0128423.
    doi: 10.1128/spectrum.01284-23pubmed: 37341610google scholar: lookup
  2. Cavalleri JV, Korbacska-Kutasi O, Leblond A, Paillot R, Pusterla N, Steinmann E, Tomlinson J. European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe.. J Vet Intern Med 2022 Nov;36(6):1858-1871.
    doi: 10.1111/jvim.16581pubmed: 36367340google scholar: lookup
  3. Pacchiarotti G, Nardini R, Scicluna MT. Equine Hepacivirus: A Systematic Review and a Meta-Analysis of Serological and Biomolecular Prevalence and a Phylogenetic Update.. Animals (Basel) 2022 Sep 20;12(19).
    doi: 10.3390/ani12192486pubmed: 36230228google scholar: lookup
  4. Gömer A, Delarocque J, Puff C, Nocke MK, Reinecke B, Baumgärtner W, Cavalleri JMV, Feige K, Steinmann E, Todt D. Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response.. Microbiol Spectr 2022 Oct 26;10(5):e0168622.
    doi: 10.1128/spectrum.01686-22pubmed: 35993785google scholar: lookup
  5. Badenhorst M, Saalmüller A, Daly JM, Ertl R, Stadler M, Puff C, de le Roi M, Baumgärtner W, Engelmann M, Brandner S, Junge HK, Pratscher B, Volz A, Saunier B, Krey T, Wittmann J, Heelemann S, Delarocque J, Wagner B, Todt D, Steinmann E, Cavalleri JV. An Equine Model for Vaccination against a Hepacivirus: Insights into Host Responses to E2 Recombinant Protein Vaccination and Subsequent Equine Hepacivirus Inoculation.. Viruses 2022 Jun 27;14(7).
    doi: 10.3390/v14071401pubmed: 35891381google scholar: lookup
  6. Gömer A, Puff C, Reinecke B, Bracht S, Conze M, Baumgärtner W, Steinmann J, Feige K, Cavalleri JMV, Steinmann E, Todt D. Experimental cross-species infection of donkeys with equine hepacivirus and analysis of host immune signatures.. One Health Outlook 2022 May 9;4(1):9.
    doi: 10.1186/s42522-022-00065-ypubmed: 35527255google scholar: lookup
  7. Gömer A, Brown RJP, Pfaender S, Deterding K, Reuter G, Orton R, Seitz S, Bock CT, Cavalleri JMV, Pietschmann T, Wedemeyer H, Steinmann E, Todt D. Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.. Virus Evol 2022;8(1):veac007.
    doi: 10.1093/ve/veac007pubmed: 35242360google scholar: lookup
  8. Hartlage AS, Kapoor A. Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up.. Viruses 2021 Aug 12;13(8).
    doi: 10.3390/v13081596pubmed: 34452460google scholar: lookup
  9. Tomlinson JE, Wolfisberg R, Fahnøe U, Patel RS, Trivedi S, Kumar A, Sharma H, Nielsen L, McDonough SP, Bukh J, Tennant BC, Kapoor A, Rosenberg BR, Rice CM, Divers TJ, Van de Walle GR, Scheel TKH. Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.. Hepatology 2021 Sep;74(3):1148-1163.
    doi: 10.1002/hep.31802pubmed: 33713356google scholar: lookup
  10. Brown RJP, Tegtmeyer B, Sheldon J, Khera T, Anggakusuma, Todt D, Vieyres G, Weller R, Joecks S, Zhang Y, Sake S, Bankwitz D, Welsch K, Ginkel C, Engelmann M, Gerold G, Steinmann E, Yuan Q, Ott M, Vondran FWR, Krey T, Ströh LJ, Miskey C, Ivics Z, Herder V, Baumgärtner W, Lauber C, Seifert M, Tarr AW, McClure CP, Randall G, Baktash Y, Ploss A, Thi VLD, Michailidis E, Saeed M, Verhoye L, Meuleman P, Goedecke N, Wirth D, Rice CM, Pietschmann T. Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice.. Sci Adv 2020 Nov;6(45).
    doi: 10.1126/sciadv.abd3233pubmed: 33148654google scholar: lookup
  11. Vengust M, Jager MC, Zalig V, Cociancich V, Laverack M, Renshaw RW, Dubovi E, Tomlinson JE, Van de Walle GR, Divers TJ. First report of equine parvovirus-hepatitis-associated Theiler's disease in Europe.. Equine Vet J 2020 Nov;52(6):841-847.
    doi: 10.1111/evj.13254pubmed: 32145096google scholar: lookup
  12. Ploss A, Kapoor A. Animal Models of Hepatitis C Virus Infection.. Cold Spring Harb Perspect Med 2020 May 1;10(5).
    doi: 10.1101/cshperspect.a036970pubmed: 31843875google scholar: lookup
  13. Pronost S, Fortier C, Marcillaud-Pitel C, Tapprest J, Foursin M, Saunier B, Pitel PH, Paillot R, Hue ES. Further Evidence for in Utero Transmission of Equine Hepacivirus to Foals.. Viruses 2019 Dec 5;11(12).
    doi: 10.3390/v11121124pubmed: 31817371google scholar: lookup
  14. Badenhorst M, de Heus P, Auer A, Rümenapf T, Tegtmeyer B, Kolodziejek J, Nowotny N, Steinmann E, Cavalleri JV. No Evidence of Mosquito Involvement in the Transmission of Equine Hepacivirus (Flaviviridae) in an Epidemiological Survey of Austrian Horses.. Viruses 2019 Nov 1;11(11).
    doi: 10.3390/v11111014pubmed: 31683893google scholar: lookup
  15. Tegtmeyer B, Echelmeyer J, Pfankuche VM, Puff C, Todt D, Fischer N, Durham A, Feige K, Baumgärtner W, Steinmann E, Cavalleri JV. Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.. Vet Med Sci 2019 Aug;5(3):372-378.
    doi: 10.1002/vms3.181pubmed: 31267690google scholar: lookup
  16. 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.
    doi: 10.1111/jvim.15368pubmed: 30520162google scholar: lookup
  17. Tomlinson JE, Tennant BC, Struzyna A, Mrad D, Browne N, Whelchel D, Johnson PJ, Jamieson C, Löhr CV, Bildfell R, McKenzie EC, Laverack M, Renshaw RW, Dubovi E, Kapoor A, Meirs RS, Belgrave R, Engiles J, Van de Walle GR, Divers TJ. Viral testing of 10 cases of Theiler's disease and 37 in-contact horses in the absence of equine biologic product administration: A prospective study (2014-2018).. J Vet Intern Med 2019 Jan;33(1):258-265.
    doi: 10.1111/jvim.15362pubmed: 30520132google scholar: lookup
  18. Lu G, Sun L, Ou J, Xu H, Wu L, Li S. Identification and genetic characterization of a novel parvovirus associated with serum hepatitis in horses in China.. Emerg Microbes Infect 2018 Oct 23;7(1):170.
    doi: 10.1038/s41426-018-0174-2pubmed: 30348940google scholar: lookup
  19. Pfankuche VM, Hahn K, Bodewes R, Hansmann F, Habierski A, Haverkamp AK, Pfaender S, Walter S, Baechlein C, Postel A, Steinmann E, Becher P, Osterhaus A, Baumgärtner W, Puff C. Comparison of Different In Situ Hybridization Techniques for the Detection of Various RNA and DNA Viruses.. Viruses 2018 Jul 20;10(7).
    doi: 10.3390/v10070384pubmed: 30037026google scholar: lookup
  20. Ramsay JD, Evanoff R, Mealey RH. Hepacivirus A Infection in Horses Defines Distinct Envelope Hypervariable Regions and Elucidates Potential Roles of Viral Strain and Adaptive Immune Status in Determining Envelope Diversity and Infection Outcome.. J Virol 2018 Sep 15;92(18).
    doi: 10.1128/JVI.00314-18pubmed: 29976666google scholar: lookup
  21. Hayashi S, Tanaka T, Moriishi K, Hirayama K, Yamada A, Hotta K. Seroepidemiology of non-primate hepacivirus (NPHV) in Japanese native horses.. J Vet Med Sci 2018 Feb 2;80(1):186-189.
    doi: 10.1292/jvms.17-0527pubmed: 29187712google scholar: lookup
  22. Trivedi S, Murthy S, Sharma H, Hartlage AS, Kumar A, Gadi SV, Simmonds P, Chauhan LV, Scheel TKH, Billerbeck E, Burbelo PD, Rice CM, Lipkin WI, Vandegrift K, Cullen JM, Kapoor A. Viral persistence, liver disease, and host response in a hepatitis C-like virus rat model.. Hepatology 2018 Aug;68(2):435-448.
    doi: 10.1002/hep.29494pubmed: 28859226google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.