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Proceedings of the National Academy of Sciences of the United States of America2013; 110(15); E1407-E1415; doi: 10.1073/pnas.1219217110

Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis.

Abstract: Theiler's disease is an acute hepatitis in horses that is associated with the administration of equine blood products; its etiologic agent has remained unknown for nearly a century. Here, we used massively parallel sequencing to explore samples from a recent Theiler's disease outbreak. Metatranscriptomic analysis of the short sequence reads identified a 10.5-kb sequence from a previously undescribed virus of the Flaviviridae family, which we designate "Theiler's disease-associated virus" (TDAV). Phylogenetic analysis clusters TDAV with GB viruses of the recently proposed Pegivirus genus, although it shares only 35.3% amino acid identity with its closest relative, GB virus D. An epidemiological survey of additional horses from three separate locations supports an association between TDAV infection and acute serum hepatitis. Experimental inoculation of horses with TDAV-positive plasma provides evidence that several weeks of viremia preceded liver injury and that liver disease may not be directly related to the level of viremia. Like hepatitis C virus, the best characterized Flaviviridae species known to cause hepatitis, we find TDAV is capable of efficient parenteral transmission, engendering acute and chronic infections associated with a diversity of clinical presentations ranging from subclinical infection to clinical hepatitis.
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Publication Date: 2013-03-18 PubMed ID: 23509292PubMed Central: PMC3625295DOI: 10.1073/pnas.1219217110Google Scholar: Lookup
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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.

This study identifies a new type of virus from the Flaviviridae family, named “Theiler’s disease-associated virus” (TDAV), that’s linked to Theiler’s disease outbreak which causes acute hepatitis in horses. The researchers found that TDAV infections occur several weeks before liver injury is observed, hinting towards a unique disease progression pattern.

Identification and Classification of TDAV

  • The research utilized advanced sequencing techniques on samples from a recent Theiler’s disease outbreak in horses. Analysis of these sequences revealed a 10.5-kb sequence from a previously unclassified virus, which the research team named “Theiler’s disease-associated virus” (TDAV).
  • Phylogenetic analysis showed that TDAV is clustered with GB viruses of the recently proposed Pegivirus genus. However, it shares a relatively low level of similarity (35.3% amino acid identity) with its closest relative, GB virus D.

Epidemiological Study and Inoculation Experiment

  • An epidemiological survey of additional horses from three different locations backed the link between TDAV infection and acute serum hepatitis, helping establish TDAV as a possible etiological agent of Theiler’s disease.
  • To further investigate the disease progression of TDAV, experimental inoculation was conducted. The researchers infected horses with TDAV-positive plasma and found that disease activity, measured by viremia, starts several weeks before any liver injury, implying a specific pathogenesis pattern of TDAV infection.

TDAV Transmission and Clinical Presentations

  • Similarly to hepatitis C virus (a well-studied member of the Flaviviridae family), TDAV showed efficient parenteral transmission, meaning it can spread effectively via direct body fluid contact.
  • The study shows that TDAV can lead to both acute and chronic infections with varying clinical presentations. These can range from subclinical infection (no visible symptoms) to clinical hepatitis, indicating a broad spectrum of disease severity associated with TDAV infection.

Cite This Article

APA
Chandriani S, Skewes-Cox P, Zhong W, Ganem DE, Divers TJ, Van Blaricum AJ, Tennant BC, Kistler AL. (2013). Identification of a previously undescribed divergent virus from the Flaviviridae family in an outbreak of equine serum hepatitis. Proc Natl Acad Sci U S A, 110(15), E1407-E1415. https://doi.org/10.1073/pnas.1219217110

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: 110
Issue: 15
Pages: E1407-E1415

Researcher Affiliations

Chandriani, Sanjay
  • Department of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608, USA.
Skewes-Cox, Peter
    Zhong, Weidong
      Ganem, Donald E
        Divers, Thomas J
          Van Blaricum, Anita J
            Tennant, Bud C
              Kistler, Amy L

                MeSH Terms

                • Animals
                • Botulinum Toxins / metabolism
                • Cluster Analysis
                • Disease Outbreaks
                • Flaviviridae / genetics
                • Flaviviridae Infections / veterinary
                • Flaviviridae Infections / virology
                • Gene Library
                • Genome, Viral
                • Hepatitis, Viral, Animal / virology
                • Horses / virology
                • Metagenomics
                • Molecular Sequence Data
                • Phylogeny
                • RNA, Viral / metabolism
                • Sequence Analysis, DNA

                Conflict of Interest Statement

                Conflict of interest statement: A.L.K., S.C., P.S.-C., T.J.D., and B.C.T. are coinventors on a patent application relating to the results herein. A.L.K., S.C., P.S.-C., D.E.G., and W.Z. are employees of the Novartis Institutes for BioMedical Research.

                References

                This article includes 42 references
                1. Kahn CM, Line S, editors. 2011. Merck Veterinary Manual (Merck, Whitehouse Station, NJ), 9th Ed. Available at www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/22802.htm.
                2. Theiler A. Acute liver-atrophy and parenchymatous hepatitis in horses. The Fifth and Sixth Reports of the Director of Veterinary Research, April, 1918 1919.
                3. Panciera RJ. Serum hepatitis in the horse. J Am Vet Med Assoc 1969;155(2):408–410.
                  pubmed: 5816124
                4. Hjerpe CA. Serum hepatitis in the horse. J Am Vet Med Assoc 1964;144:734–740.
                  pubmed: 14156990
                5. Aleman M, Nieto JE, Carr EA, Carlson GP. Serum hepatitis associated with commercial plasma transfusion in horses. J Vet Intern Med 2005;19(1):120–122.
                  pubmed: 15715060
                6. Guglick MA, MacAllister CG, Ely RW, Edwards WC. Hepatic disease associated with administration of tetanus antitoxin in eight horses. J Am Vet Med Assoc 1995;206(11):1737–1740.
                  pubmed: 7782247
                7. Divers TJ. Acute hepatic failure (Theiler’s disease). Current Therapy in Equine Medicine 1987;2nd Ed:pp. 110–112.
                8. Thomsett LR. Acute hepatic failure in the horse. Equine Vet J 1971;3(1):15–19.
                  pubmed: 5161355
                9. Cox HR, Philip CB, Marsh H, Kilpatrick JW. Observations incident to an outbreak of equine encephalomyelitis in the Bitterroot valley of western Montana. J Am Vet Med Assoc 1938;93:225–232.
                10. Herniou EA, Olszewski JA, O’Reilly DR, Cory JS. Ancient coevolution of baculoviruses and their insect hosts. J Virol 2004;78(7):3244–3251.
                  pmc: PMC371050pubmed: 15016845
                11. Graham FL, Smiley J, Russell WC, Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 1977;36(1):59–74.
                  pubmed: 886304
                12. Solnick D. Construction of an adenovirus-SV40 recombinant producing SV40 T antigen from an adenovirus late promoter. Cell 1981;24(1):135–143.
                  pubmed: 6263482
                13. Thummel C, Tjian R, Grodzicker T. Expression of SV40 T antigen under control of adenovirus promoters. Cell 1981;23(3):825–836.
                  pubmed: 7226231
                14. Borchers K. Virological and molecular biological investigations into equine herpes virus type 2 (EHV-2) experimental infections. Virus Res 1998;55(1):101–106.
                  pubmed: 9712516
                15. Kemeny L, Pearson JE. Isolation of herpesvirus from equine leukocytes: Comparison with equine rhinopneumonitis virus. Can J Comp Med 1970;34(1):59–65.
                  pmc: PMC1319423pubmed: 4246005
                16. Earl D. Assemblathon 1: A competitive assessment of de novo short read assembly methods. Genome Res 2011;21(12):2224–2241.
                  pmc: PMC3227110pubmed: 21926179
                17. Epstein JH. Identification of GBV-D, a novel GB-like flavivirus from old world frugivorous bats (Pteropus giganteus) in Bangladesh. PLoS Pathog 2010;6:e1000972.
                  pmc: PMC2895649pubmed: 20617167
                18. Cha TA. At least five related, but distinct, hepatitis C viral genotypes exist. Proc Natl Acad Sci USA 1992;89(15):7144–7148.
                  pmc: PMC49662pubmed: 1323128
                19. Burbelo PD. Serology-enabled discovery of genetically diverse hepaciviruses in a new host. J Virol 2012;86(11):6171–6178.
                  pmc: PMC3372197pubmed: 22491452
                20. Stapleton JT, Foung S, Muerhoff AS, Bukh J, Simmonds P. 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 2011;92(Pt 2):233–246.
                  pmc: PMC3081076pubmed: 21084497
                21. Lyons S. Nonprimate hepaciviruses in domestic horses, United Kingdom. Emerg Infect Dis 2012;18(12):1976–1982.
                  pmc: PMC3557883pubmed: 23171728
                22. Huang L. Hepatitis C virus nonstructural protein 5A (NS5A) is an RNA-binding protein. J Biol Chem 2005;280(43):36417–36428.
                  pubmed: 16126720
                23. Lohmann V, Körner F, Dobierzewska A, Bartenschlager R. Mutations in hepatitis C virus RNAs conferring cell culture adaptation. J Virol 2001;75(3):1437–1449.
                  pmc: PMC114050pubmed: 11152517
                24. Macdonald A, Harris M. Hepatitis C virus NS5A: Tales of a promiscuous protein. J Gen Virol 2004;85(Pt 9):2485–2502.
                  pubmed: 15302943
                25. Gao M. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 2010;465(7294):96–100.
                  pmc: PMC7094952pubmed: 20410884
                26. Tellinghuisen TL, Marcotrigiano J, Rice CM. Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase. Nature 2005;435(7040):374–379.
                  pmc: PMC1440517pubmed: 15902263
                27. Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM. The NS5A protein of hepatitis C virus is a zinc metalloprotein. J Biol Chem 2004;279(47):48576–48587.
                  pubmed: 15339921
                28. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005;309(5740):1577–1581.
                  pubmed: 16141076
                29. Kapoor A. Characterization of a canine homolog of hepatitis C virus. Proc Natl Acad Sci USA 2011;108(28):11608–11613.
                  pmc: PMC3136326pubmed: 21610165
                30. Esteban JI. Evaluation of antibodies to hepatitis C virus in a study of transfusion-associated hepatitis. N Engl J Med 1990;323(16):1107–1112.
                  pubmed: 2170839
                31. Uto H, Mawatari S, Kumagai K, Ido A, Tsubouchi H. Clinical features of hepatitis C virus carriers with persistently normal alanine aminotransferase levels. Hepat Mon 2012;12(2):77–84.
                  pmc: PMC3321325pubmed: 22509183
                32. Armstrong GL. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144(10):705–714.
                  pubmed: 16702586
                33. Alter MJ. HCV routes of transmission: What goes around comes around. Semin Liver Dis 2011;31(4):340–346.
                  pubmed: 22189974
                34. Anand B-S, Velez M. Assessment of correlation between serum titers of hepatitis C virus and severity of liver disease. World J Gastroenterol 2004;10(16):2409–2411.
                  pmc: PMC4576299pubmed: 15285030
                35. Puoti C. Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels. Hepatology 1997;26(6):1393–1398.
                  pubmed: 9397976
                36. Lavanchy D. The global burden of hepatitis C. Liver Int 2009;29(Suppl 1):74–81.
                  pubmed: 19207969
                37. Runckel C. Temporal analysis of the honey bee microbiome reveals four novel viruses and seasonal prevalence of known viruses, Nosema, and Crithidia. PLoS ONE 2011;6(6):e20656.
                  pmc: PMC3110205pubmed: 21687739
                38. Welch TA. A technique for high-performance data compression. Computer 1984;17:8–19.
                39. Wade CM. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 2009;326(5954):865–867.
                  pmc: PMC3785132pubmed: 19892987
                40. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990;215(3):403–410.
                  pubmed: 2231712
                41. Edgar RC. MUSCLE: Multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004;32(5):1792–1797.
                  pmc: PMC390337pubmed: 15034147
                42. Tamura K. MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011;28(10):2731–2739.
                  pmc: PMC3203626pubmed: 21546353

                Citations

                This article has been cited 77 times.
                1. Xu W, Wang W, Liu Q. Identification of a novel pegivirus in reindeer (Rangifer tarandus valentinae) in Northeastern China. BMC Vet Res 2025 Dec 2;22(1):9.
                  doi: 10.1186/s12917-025-05167-zpubmed: 41331462google scholar: lookup
                2. Ricci I, Rosone F, Pacchiarotti G, Manna G, Cersini A, Carvelli A, La Rocca D, Cammalleri E, Giordani R, Tofani S, Conti R, Rombolà P, Nardini R, Minniti CA, Caforio R, Linardi B, Scicluna MT. Pegiviruses and Coronavirus: Biomolecular Prevalence and Phylogenetic Analysis of Strains Detected in Italian Horse Populations. Viruses 2025 Aug 2;17(8).
                  doi: 10.3390/v17081076pubmed: 40872790google scholar: lookup
                3. 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.
                  doi: 10.1155/2023/5251034pubmed: 40303682google scholar: lookup
                4. Blomström AL, Källse A, Riihimäki M. Detection and genetic characterization of equine viruses in Sweden using viral metagenomics. BMC Vet Res 2025 Feb 27;21(1):119.
                  doi: 10.1186/s12917-025-04613-2pubmed: 40011862google scholar: lookup
                5. Mazzei M, Sorvillo B, Sgorbini M, Bindi F, Perelli A, Laus F. The Role of Viral Pathogens in Horse Respiratory Diseases: A Cytological and Molecular Approach Using Next-Generation Sequencing. Animals (Basel) 2024 Nov 21;14(23).
                  doi: 10.3390/ani14233347pubmed: 39682313google scholar: lookup
                6. Fortier C, El-Hage C, Normand C, Hue ES, Sutton G, Marcillaud-Pitel C, Jeffers K, Bamford N, Oden E, Paillot R, Hartley C, Gilkerson J, Pronost S. Detection of Equine Parvovirus-Hepatitis Virus and Equine Hepacivirus in Archived Sera from Horses in France and Australia. Viruses 2024 May 28;16(6).
                  doi: 10.3390/v16060862pubmed: 38932156google scholar: lookup
                7. Kandathil AJ, Thomas DL. The Blood Virome: A new frontier in biomedical science. Biomed Pharmacother 2024 Jun;175:116608.
                  doi: 10.1016/j.biopha.2024.116608pubmed: 38703502google scholar: lookup
                8. Tomal A, Szłapka-Kosarzewska J, Mironiuk M, Michalak I, Marycz K. Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions improves insulin sensitivity and reduces systemic inflammation in equine metabolic affected horses. Front Endocrinol (Lausanne) 2024;15:1382844.
                  doi: 10.3389/fendo.2024.1382844pubmed: 38689728google scholar: lookup
                9. Schwarz ER, Long MT. Comparison of West Nile Virus Disease in Humans and Horses: Exploiting Similarities for Enhancing Syndromic Surveillance. Viruses 2023 May 24;15(6).
                  doi: 10.3390/v15061230pubmed: 37376530google scholar: lookup
                10. Tomlinson JE, Van de Walle GR. Nasal transmission of equine parvovirus hepatitis. J Vet Intern Med 2022 Nov;36(6):2238-2244.
                  doi: 10.1111/jvim.16569pubmed: 36250682google scholar: lookup
                11. Chen S, Wang H, Dzakah EE, Rashid F, Wang J, Tang S. The Second Human Pegivirus, a Non-Pathogenic RNA Virus with Low Prevalence and Minimal Genetic Diversity. Viruses 2022 Aug 23;14(9).
                  doi: 10.3390/v14091844pubmed: 36146649google scholar: lookup
                12. Stapleton JT. Human Pegivirus Type 1: A Common Human Virus That Is Beneficial in Immune-Mediated Disease?. Front Immunol 2022;13:887760.
                  doi: 10.3389/fimmu.2022.887760pubmed: 35707535google scholar: lookup
                13. Chang WS, Rose K, Holmes EC. Meta-transcriptomic analysis of the virome and microbiome of the invasive Indian myna (Acridotheres tristis) in Australia. One Health 2021 Dec;13:100360.
                  doi: 10.1016/j.onehlt.2021.100360pubmed: 34917744google scholar: lookup
                14. Cebriá-Mendoza M, Bracho MA, Arbona C, Larrea L, Díaz W, Sanjuán R, Cuevas JM. Exploring the Diversity of the Human Blood Virome. Viruses 2021 Nov 21;13(11).
                  doi: 10.3390/v13112322pubmed: 34835128google scholar: lookup
                15. Lee SK, Park D, Lee I. Molecular Prevalence of Equine Parvovirus-Hepatitis in the Sera of Clinically Healthy Horses in South Korea. Vet Sci 2021 Nov 19;8(11).
                  doi: 10.3390/vetsci8110282pubmed: 34822655google scholar: lookup
                16. Yoon J, Park T, Kim A, Park J, Park BJ, Ahn HS, Go HJ, Kim DH, Jung S, Seo Y, Lee JB, Park SY, Song CS, Lee SW, Choi IS. First Clinical Case of Equine Parvovirus-Hepatitis-Related Theiler's Disease in Asia. Viruses 2021 Sep 24;13(10).
                  doi: 10.3390/v13101917pubmed: 34696347google scholar: lookup
                17. Altan E, Hui A, Li Y, Pesavento P, Asín J, Crossley B, Deng X, Uzal FA, Delwart E. New Parvoviruses and Picornavirus in Tissues and Feces of Foals with Interstitial Pneumonia. Viruses 2021 Aug 14;13(8).
                  doi: 10.3390/v13081612pubmed: 34452477google scholar: lookup
                18. Zehetner V, Cavalleri JV, Klang A, Hofer M, Preining I, Steinborn R, Ramsauer AS. Equine Parvovirus-Hepatitis Screening in Horses and Donkeys with Histopathologic Liver Abnormalities. Viruses 2021 Aug 12;13(8).
                  doi: 10.3390/v13081599pubmed: 34452465google scholar: lookup
                19. Reinecke B, Klöhn M, Brüggemann Y, Kinast V, Todt D, Stang A, Badenhorst M, Koeppel K, Guthrie A, Groner U, Puff C, de le Roi M, Baumgärtner W, Cavalleri JV, Steinmann E. Clinical Course of Infection and Cross-Species Detection of Equine Parvovirus-Hepatitis. Viruses 2021 Jul 26;13(8).
                  doi: 10.3390/v13081454pubmed: 34452320google scholar: lookup
                20. Sims S, Michaelsen K, Burkhard S, Fraefel C. In Vitro Comparison of the Internal Ribosomal Entry Site Activity from Rodent Hepacivirus and Pegivirus and Construction of Pseudoparticles. Adv Virol 2021;2021:5569844.
                  doi: 10.1155/2021/5569844pubmed: 34422054google scholar: lookup
                21. Ramsauer AS, Badenhorst M, Cavalleri JV. Equine parvovirus hepatitis. Equine Vet J 2021 Sep;53(5):886-894.
                  doi: 10.1111/evj.13477pubmed: 34101906google scholar: lookup
                22. Badenhorst M, de Heus P, Auer A, Tegtmeyer B, Stang A, Dimmel K, Tichy A, Kubacki J, Bachofen C, Steinmann E, Cavalleri JMV. Active equine parvovirus-hepatitis infection is most frequently detected in Austrian horses of advanced age. Equine Vet J 2022 Mar;54(2):379-389.
                  doi: 10.1111/evj.13444pubmed: 33704819google scholar: lookup
                23. Porter AF, Pettersson JH, Chang WS, Harvey E, Rose K, Shi M, Eden JS, Buchmann J, Moritz C, Holmes EC. Novel hepaci- and pegi-like viruses in native Australian wildlife and non-human primates. Virus Evol 2020 Jul;6(2):veaa064.
                  doi: 10.1093/ve/veaa064pubmed: 33240526google scholar: lookup
                24. Zhu N, Xu R, Tang W, Wang H, Wan Z, Wu X, Fu Y, Tang S, Yu S. [Detection of a novel human pegivirus HPgV-2 in healthy blood donors and recipients of multiple transfusions: implications for blood safety]. Nan Fang Yi Ke Da Xue Xue Bao 2018 Jul 30;38(7):842-849.
                  doi: 10.3969/j.issn.1673-4254.2018.07.12pubmed: 33168509google scholar: lookup
                25. Momoi Y, Matsuu A. Detection of severe fever with thrombocytopenia syndrome virus and other viruses in cats via unbiased next-generation sequencing. J Vet Diagn Invest 2021 Mar;33(2):279-282.
                  doi: 10.1177/1040638720967506pubmed: 33084531google scholar: lookup
                26. Heffron AS, Lauck M, Somsen ED, Townsend EC, Bailey AL, Sosa M, Eickhoff J, Capuano Iii S, Newman CM, Kuhn JH, Mejia A, Simmons HA, O'Connor DH. Discovery of a Novel Simian Pegivirus in Common Marmosets (Callithrix jacchus) with Lymphocytic Enterocolitis. Microorganisms 2020 Sep 30;8(10).
                  doi: 10.3390/microorganisms8101509pubmed: 33007921google scholar: lookup
                27. Wu Z, Wu Y, Zhang W, Merits A, Simmonds P, Wang M, Jia R, Zhu D, Liu M, Zhao X, Yang Q, Wu Y, Zhang S, Huang J, Ou X, Mao S, Liu Y, Zhang L, Yu Y, Tian B, Pan L, Rehman MU, Chen S, Cheng A. The First Nonmammalian Pegivirus Demonstrates Efficient In Vitro Replication and High Lymphotropism. J Virol 2020 Sep 29;94(20).
                  doi: 10.1128/JVI.01150-20pubmed: 32759314google scholar: lookup
                28. Tomlinson JE, Wolfisberg R, Fahnøe U, Sharma H, Renshaw RW, Nielsen L, Nishiuchi E, Holm C, Dubovi E, Rosenberg BR, Tennant BC, Bukh J, Kapoor A, Divers TJ, Rice CM, Van de Walle GR, Scheel TKH. Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. PLoS Pathog 2020 Jul;16(7):e1008677.
                  doi: 10.1371/journal.ppat.1008677pubmed: 32649726google scholar: lookup
                29. Xie Y, Wang X, Feng J, Wei L, Li G, Si G, Chen Y, Yan H, He D. The Prevalence, Genetic Characterization, and Evolutionary Analysis of Porcine Pegivirus in Guangdong, China. Virol Sin 2021 Feb;36(1):52-60.
                  doi: 10.1007/s12250-020-00240-3pubmed: 32643050google scholar: lookup
                30. Arhab Y, Bulakhov AG, Pestova TV, Hellen CUT. Dissemination of Internal Ribosomal Entry Sites (IRES) Between Viruses by Horizontal Gene Transfer. Viruses 2020 Jun 4;12(6).
                  doi: 10.3390/v12060612pubmed: 32512856google scholar: lookup
                31. Lu G, Wu L, Ou J, Li S. Equine Parvovirus-Hepatitis in China: Characterization of Its Genetic Diversity and Evidence for Natural Recombination Events Between the Chinese and American Strains. Front Vet Sci 2020;7:121.
                  doi: 10.3389/fvets.2020.00121pubmed: 32211433google scholar: lookup
                32. 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
                33. Wan Z, Liu J, Hu F, Shui J, Li L, Wang H, Tang X, Hu C, Liang Y, Zhou Y, Cai W, Tang S. Evidence that the second human pegivirus (HPgV-2) is primarily a lymphotropic virus and can replicate independent of HCV replication. Emerg Microbes Infect 2020;9(1):485-495.
                  doi: 10.1080/22221751.2020.1730247pubmed: 32100631google scholar: lookup
                34. Mrzljak A, Tabain I, Premac H, Bogdanic M, Barbic L, Savic V, Stevanovic V, Jelic A, Mikulic D, Vilibic-Cavlek T. The Role of Emerging and Neglected Viruses in the Etiology of Hepatitis. Curr Infect Dis Rep 2019 Nov 21;21(12):51.
                  doi: 10.1007/s11908-019-0709-2pubmed: 31754812google scholar: lookup
                35. Meister TL, Tegtmeyer B, Brüggemann Y, Sieme H, Feige K, Todt D, Stang A, Cavalleri JV, Steinmann E. Characterization of Equine Parvovirus in Thoroughbred Breeding Horses from Germany. Viruses 2019 Oct 18;11(10).
                  doi: 10.3390/v11100965pubmed: 31635426google scholar: lookup
                36. Altan E, Li Y, Sabino-Santos G Jr, Sawaswong V, Barnum S, Pusterla N, Deng X, Delwart E. Viruses in Horses with Neurologic and Respiratory Diseases. Viruses 2019 Oct 14;11(10).
                  doi: 10.3390/v11100942pubmed: 31614994google scholar: lookup
                37. Kennedy J, Pfankuche VM, Hoeltig D, Postel A, Keuling O, Ciurkiewicz M, Baumgärtner W, Becher P, Baechlein C. Genetic variability of porcine pegivirus in pigs from Europe and China and insights into tissue tropism. Sci Rep 2019 Jun 3;9(1):8174.
                  doi: 10.1038/s41598-019-44642-0pubmed: 31160748google scholar: lookup
                38. Meister TL, Tegtmeyer B, Postel A, Cavalleri JV, Todt D, Stang A, Steinmann E. Equine Parvovirus-Hepatitis Frequently Detectable in Commercial Equine Serum Pools. Viruses 2019 May 21;11(5).
                  doi: 10.3390/v11050461pubmed: 31117220google scholar: lookup
                39. Lei D, Ye Y, Lin K, Zhang F, Huang D, Li K, Yuan W, Wu Q, Ding Z, Wang L, Song D, Tang Y. Detection and genetic characterization of porcine pegivirus from pigs in China. Virus Genes 2019 Apr;55(2):248-252.
                  doi: 10.1007/s11262-018-1624-6pubmed: 30600430google scholar: lookup
                40. 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
                41. 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
                42. 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
                43. Divers TJ, Tennant BC, Kumar A, McDonough S, Cullen J, Bhuva N, Jain K, Chauhan LS, Scheel TKH, Lipkin WI, Laverack M, Trivedi S, Srinivasa S, Beard L, Rice CM, Burbelo PD, Renshaw RW, Dubovi E, Kapoor A. New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product. Emerg Infect Dis 2018 Feb;24(2):303-310.
                  doi: 10.3201/eid2402.171031pubmed: 29350162google scholar: lookup
                44. Lu G, Huang J, Yang Q, Xu H, Wu P, Fu C, Li S. Identification and genetic characterization of hepacivirus and pegivirus in commercial equine serum products in China. PLoS One 2017;12(12):e0189208.
                  doi: 10.1371/journal.pone.0189208pubmed: 29216266google scholar: lookup
                45. Kumar A, Murthy S, Kapoor A. Evolution of selective-sequencing approaches for virus discovery and virome analysis. Virus Res 2017 Jul 15;239:172-179.
                  doi: 10.1016/j.virusres.2017.06.005pubmed: 28583442google scholar: lookup
                46. Tsunoda I, Omura S, Sato F, Kusunoki S, Fujita M, Park AM, Hasanovic F, Yanagihara R, Nagata S. Neuropathogenesis of Zika Virus Infection : Potential Roles of Antibody-Mediated Pathology. Acta Med Kinki Univ 2016;41(2):37-52.
                  pubmed: 28428682
                47. Dimitrov KM, Sharma P, Volkening JD, Goraichuk IV, Wajid A, Rehmani SF, Basharat A, Shittu I, Joannis TM, Miller PJ, Afonso CL. A robust and cost-effective approach to sequence and analyze complete genomes of small RNA viruses. Virol J 2017 Apr 7;14(1):72.
                  doi: 10.1186/s12985-017-0741-5pubmed: 28388925google scholar: lookup
                48. Hartlage AS, Cullen JM, Kapoor A. The Strange, Expanding World of Animal Hepaciviruses. Annu Rev Virol 2016 Sep 29;3(1):53-75.
                  doi: 10.1146/annurev-virology-100114-055104pubmed: 27741408google scholar: lookup
                49. Smith DB, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff AS, Pletnev A, Rico-Hesse R, Stapleton JT, Simmonds P. Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family. J Gen Virol 2016 Nov;97(11):2894-2907.
                  doi: 10.1099/jgv.0.000612pubmed: 27692039google scholar: lookup
                50. Baechlein C, Grundhoff A, Fischer N, Alawi M, Hoeltig D, Waldmann KH, Becher P. Pegivirus Infection in Domestic Pigs, Germany. Emerg Infect Dis 2016 Jul;22(7):1312-4.
                  doi: 10.3201/eid2207.160024pubmed: 27314228google scholar: lookup
                51. Lu G, Sun L, Xu T, He D, Wang Z, Ou S, Jia K, Yuan L, Li S. 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 2016;11(5):e0155662.
                  doi: 10.1371/journal.pone.0155662pubmed: 27182887google scholar: lookup
                52. Berg MG, Lee D, Coller K, Frankel M, Aronsohn A, Cheng K, Forberg K, Marcinkus M, Naccache SN, Dawson G, Brennan C, Jensen DM, Hackett J Jr, Chiu CY. Discovery of a Novel Human Pegivirus in Blood Associated with Hepatitis C Virus Co-Infection. PLoS Pathog 2015 Dec;11(12):e1005325.
                  doi: 10.1371/journal.ppat.1005325pubmed: 26658760google scholar: lookup
                53. Hansen TA, Fridholm H, Frøslev TG, Kjartansdóttir KR, Willerslev E, Nielsen LP, Hansen AJ. New Type of Papillomavirus and Novel Circular Single Stranded DNA Virus Discovered in Urban Rattus norvegicus Using Circular DNA Enrichment and Metagenomics. PLoS One 2015;10(11):e0141952.
                  doi: 10.1371/journal.pone.0141952pubmed: 26559957google scholar: lookup
                54. 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.
                  doi: 10.1093/gbe/evv202pubmed: 26494702google scholar: lookup
                55. 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.
                  doi: 10.1128/JVI.02036-15pubmed: 26491167google scholar: lookup
                56. Kapoor A, Kumar A, Simmonds P, Bhuva N, Singh Chauhan L, Lee B, Sall AA, Jin Z, Morse SS, Shaz B, Burbelo PD, Lipkin WI. Virome Analysis of Transfusion Recipients Reveals a Novel Human Virus That Shares Genomic Features with Hepaciviruses and Pegiviruses. mBio 2015 Sep 22;6(5):e01466-15.
                  doi: 10.1128/mBio.01466-15pubmed: 26396247google scholar: lookup
                57. Vercauteren K, de Jong YP, Meuleman P. Animal models for the study of HCV. Curr Opin Virol 2015 Aug;13:67-74.
                  doi: 10.1016/j.coviro.2015.04.009pubmed: 26304554google scholar: lookup
                58. Daly GM, Leggett RM, Rowe W, Stubbs S, Wilkinson M, Ramirez-Gonzalez RH, Caccamo M, Bernal W, Heeney JL. Host Subtraction, Filtering and Assembly Validations for Novel Viral Discovery Using Next Generation Sequencing Data. PLoS One 2015;10(6):e0129059.
                  doi: 10.1371/journal.pone.0129059pubmed: 26098299google scholar: lookup
                59. Li L, Giannitti F, Low J, Keyes C, Ullmann LS, Deng X, Aleman M, Pesavento PA, Pusterla N, Delwart E. Exploring the virome of diseased horses. J Gen Virol 2015 Sep;96(9):2721-2733.
                  doi: 10.1099/vir.0.000199pubmed: 26044792google scholar: lookup
                60. 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.
                  doi: 10.1099/vir.0.000208pubmed: 26041875google scholar: lookup
                61. Pfaender S, Brown RJ, Pietschmann T, Steinmann E. Natural reservoirs for homologs of hepatitis C virus. Emerg Microbes Infect 2014 Mar;3(3):e21.
                  doi: 10.1038/emi.2014.19pubmed: 26038514google scholar: lookup
                62. 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.
                  doi: 10.1128/JVI.00534-15pubmed: 25926652google scholar: lookup
                63. Jensen RH, Mollerup S, Mourier T, Hansen TA, Fridholm H, Nielsen LP, Willerslev E, Hansen AJ, Vinner L. Target-dependent enrichment of virions determines the reduction of high-throughput sequencing in virus discovery. PLoS One 2015;10(4):e0122636.
                  doi: 10.1371/journal.pone.0122636pubmed: 25853649google scholar: lookup
                64. 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.
                  doi: 10.1073/pnas.1500265112pubmed: 25646476google scholar: lookup
                65. 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.
                  doi: 10.1016/j.antiviral.2014.12.014pubmed: 25545071google scholar: lookup
                66. Strong MJ, Lin Z, Flemington EK. Expanding the conversation on high-throughput virome sequencing standards to include consideration of microbial contamination sources. mBio 2014 Oct 28;5(6):e01989.
                  doi: 10.1128/mBio.01989-14pubmed: 25352620google scholar: lookup
                67. Stapleton JT, Xiang J, McLinden JH, Bhattarai N, Chivero ET, Klinzman D, Kaufman TM, Chang Q. A novel T cell evasion mechanism in persistent RNA virus infection. Trans Am Clin Climatol Assoc 2014;125:14-24; discussion 24-6.
                  pubmed: 25125715
                68. Sibley SD, Lauck M, Bailey AL, Hyeroba D, Tumukunde A, Weny G, Chapman CA, O'Connor DH, Goldberg TL, Friedrich TC. Discovery and characterization of distinct simian pegiviruses in three wild African Old World monkey species. PLoS One 2014;9(2):e98569.
                  doi: 10.1371/journal.pone.0098569pubmed: 24918769google scholar: lookup
                69. Kao RR, Haydon DT, Lycett SJ, Murcia PR. Supersize me: how whole-genome sequencing and big data are transforming epidemiology. Trends Microbiol 2014 May;22(5):282-91.
                  doi: 10.1016/j.tim.2014.02.011pubmed: 24661923google scholar: lookup
                70. Ghai RR, Sibley SD, Lauck M, Dinis JM, Bailey AL, Chapman CA, Omeja P, Friedrich TC, O'Connor DH, Goldberg TL. Deep sequencing identifies two genotypes and high viral genetic diversity of human pegivirus (GB virus C) in rural Ugandan patients. J Gen Virol 2013 Dec;94(Pt 12):2670-2678.
                  doi: 10.1099/vir.0.055509-0pubmed: 24077364google scholar: lookup
                71. Naccache SN, Greninger AL, Lee D, Coffey LL, Phan T, Rein-Weston A, Aronsohn A, Hackett J Jr, Delwart EL, Chiu CY. The perils of pathogen discovery: origin of a novel parvovirus-like hybrid genome traced to nucleic acid extraction spin columns. J Virol 2013 Nov;87(22):11966-77.
                  doi: 10.1128/JVI.02323-13pubmed: 24027301google scholar: lookup
                72. Stewart H, Walter C, Jones D, Lyons S, Simmonds P, Harris M. The non-primate hepacivirus 5' untranslated region possesses internal ribosomal entry site activity. J Gen Virol 2013 Dec;94(Pt 12):2657-2663.
                  doi: 10.1099/vir.0.055764-0pubmed: 24026670google scholar: lookup
                73. 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.
                  doi: 10.1128/JVI.00888-13pubmed: 23740998google scholar: lookup
                74. Chiu CY. Viral pathogen discovery. Curr Opin Microbiol 2013 Aug;16(4):468-78.
                  doi: 10.1016/j.mib.2013.05.001pubmed: 23725672google scholar: lookup
                75. Chiu C. The hidden threat of unidentified agents of disease in human and veterinary biologicals. Biologicals 2013 May;41(3):129-30.
                  doi: 10.1016/j.biologicals.2013.03.004pubmed: 23622811google scholar: lookup
                76. Kapoor A, Simmonds P, Cullen JM, Scheel TK, Medina JL, Giannitti F, Nishiuchi E, Brock KV, Burbelo PD, Rice CM, Lipkin WI. Identification of a pegivirus (GB virus-like virus) that infects horses. J Virol 2013 Jun;87(12):7185-90.
                  doi: 10.1128/JVI.00324-13pubmed: 23596285google scholar: lookup
                77. Ruby JG, Bellare P, Derisi JL. PRICE: software for the targeted assembly of components of (Meta) genomic sequence data. G3 (Bethesda) 2013 May 20;3(5):865-80.
                  doi: 10.1534/g3.113.005967pubmed: 23550143google scholar: lookup
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