FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of virology2019; 93(12); doi: 10.1128/JVI.00045-19

Intrahost Selection Pressure Drives Equine Arteritis Virus Evolution during Persistent Infection in the Stallion Reproductive Tract.

Abstract: Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a reproductive and respiratory disease of horses. Following natural infection, 10 to 70% of infected stallions can become carriers of EAV and continue to shed virus in the semen. In this study, sequential viruses isolated from nasal secretions, buffy coat cells, and semen of seven experimentally infected and two naturally infected EAV carrier stallions were deep sequenced to elucidate the intrahost microevolutionary process after a single transmission event. Analysis of variants from nasal secretions and buffy coat cells lacked extensive positive selection; however, characteristics of the mutant spectra were different in the two sample types. In contrast, the initial semen virus populations during acute infection have undergone a selective bottleneck, as reflected by the reduction in population size and diversifying selection at multiple sites in the viral genome. Furthermore, during persistent infection, extensive genome-wide purifying selection shaped variant diversity in the stallion reproductive tract. Overall, the nonstochastic nature of EAV evolution during persistent infection was driven by active intrahost selection pressure. Among the open reading frames within the viral genome, ORF3, ORF5, and the nsp2-coding region of ORF1a accumulated the majority of nucleotide substitutions during persistence, with ORF3 and ORF5 having the highest intrahost evolutionary rates. The findings presented here provide a novel insight into the evolutionary mechanisms of EAV and identified critical regions of the viral genome likely associated with the establishment and maintenance of persistent infection in the stallion reproductive tract.IMPORTANCE EAV can persist in the reproductive tract of infected stallions, and consequently, long-term carrier stallions constitute its sole natural reservoir. Previous studies demonstrated that the ampullae of the vas deferens are the primary site of viral persistence in the stallion reproductive tract and the persistence is associated with a significant inflammatory response that is unable to clear the infection. This is the first study that describes EAV full-length genomic evolution during acute and long-term persistent infection in the stallion reproductive tract using next-generation sequencing and contemporary sequence analysis techniques. The data provide novel insight into the intrahost evolution of EAV during acute and persistent infection and demonstrate that persistent infection is characterized by extensive genome-wide purifying selection and a nonstochastic evolutionary pattern mediated by intrahost selective pressure, with important nucleotide substitutions occurring in ORF1a (region encoding nsp2), ORF3, and ORF5.
Copyright © 2019 American Society for Microbiology.
Get Full Text
Publication Date: 2019-05-29 PubMed ID: 30918077PubMed Central: PMC6613756DOI: 10.1128/JVI.00045-19Google 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
  • Non-U.S. Gov't
  • 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 research investigates how the equine arteritis virus (EAV), responsible for a reproductive and respiratory disease in horses, evolves during persistent infection in the stallion reproductive tract. The study used deep sequencing on viruses extracted from various tissues of experimentally and naturally infected stallions. The researchers discovered that the virus evolution is not random and is driven by active selection pressure within the host. Key changes during this evolution are occurring in specific regions of the viral genome.

Research Methodology

  • The study subjects included seven experimentally infected and two naturally infected stallion carriers of EAV.
  • The researchers used deep sequencing to create a detailed genetic profile of the EAV isolates obtained from the nasal secretions, buffy coat cells, and semen of these infection carriers.
  • The intrahost microevolutionary process of the virus post a single transmission event was examined and analysed in-depth.

Key Findings

  • The study found that while nasal secretions and buffy coat cells showed no evidence of extensive positive selection, the mutant spectra between the two sample types differed.
  • At the initial stage of acute infection, the virus populations in the semen underwent a “selective bottleneck”, where the population size reduced, and the viral genome experienced diversifying selection at multiple sites.
  • During persistent infection, the variant diversity was shaped extensively by genome-wide purifying selection.
  • It was also observed that EAV evolution during persistent infection is not random but driven by intrahost selection pressure.
  • Key changes were noted in the open reading frames within the viral genome, with the majority of nucleotide substitutions occurring in ORF3, ORF5, and the nsp2-coding region of ORF1a. These areas have the highest intrahost evolutionary rates.

Significance of the Study

  • This study was the first to assess the full genomic evolution of EAV during acute and long-term persistence in the stallion reproductive tract using contemporary sequence analysis techniques along with next-generation sequencing.
  • The findings can provide new insights into the intrahost evolution of EAV during acute and persistent infection.
  • This study demonstrates that persistent infection is characterized by extensive genome-wide purifying selection and a nonrandom evolutionary pattern driven by intrahost selective pressure.
  • Understanding these patterns could be crucial while studying specific virus transmissions or designing targeted antiviral strategies.

Cite This Article

APA
Nam B, Mekuria Z, Carossino M, Li G, Zheng Y, Zhang J, Cook RF, Shuck KM, Campos JR, Squires EL, Troedsson MHT, Timoney PJ, Balasuriya UBR. (2019). Intrahost Selection Pressure Drives Equine Arteritis Virus Evolution during Persistent Infection in the Stallion Reproductive Tract. J Virol, 93(12). https://doi.org/10.1128/JVI.00045-19

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 93
Issue: 12

Researcher Affiliations

Nam, Bora
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Mekuria, Zelalem
  • Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA zmekuria1@lsu.edu balasuriya1@lsu.edu.
Carossino, Mariano
  • Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Li, Ganwu
  • Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
Zheng, Ying
  • Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
Zhang, Jianqiang
  • Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
Cook, R Frank
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Shuck, Kathleen M
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Campos, Juliana R
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Squires, Edward L
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Troedsson, Mats H T
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Timoney, Peter J
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
Balasuriya, Udeni B R
  • Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA zmekuria1@lsu.edu balasuriya1@lsu.edu.

MeSH Terms

  • Amino Acid Sequence / genetics
  • Animals
  • Arterivirus Infections / genetics
  • Arterivirus Infections / virology
  • Base Sequence / genetics
  • Carrier State / virology
  • Equartevirus / genetics
  • Equartevirus / metabolism
  • Equartevirus / pathogenicity
  • Evolution, Molecular
  • Genome, Viral / genetics
  • Horse Diseases / virology
  • Horses / genetics
  • Host-Pathogen Interactions / genetics
  • Male
  • Open Reading Frames / genetics
  • Phylogeny
  • Semen / virology
  • Sequence Analysis / methods

References

This article includes 93 references
  1. Stadejek T, Mittelholzer C, Oleksiewicz MB, Paweska J, Belák S. Highly diverse type of equine arteritis virus (EAV) from the semen of a South African donkey: short communication. Acta Vet Hung 54:263–270.
    doi: 10.1556/AVet.54.2006.2.12pubmed: 16841763google scholar: lookup
  2. Paweska J. Equine viral arteritis in donkeys in South Africa. J S Afr Vet Assoc 65:40.
    pubmed: 7776331
  3. Paweska J, Barnard B. Serological evidence of equine arteritis virus in donkeys in South Africa. Onderstepoort J Vet Res 60:155–158.
    pubmed: 8392682
  4. Timoney PJ, McCollum WH. Equine viral arteritis. Vet Clin North Am Equine Pract 9:295–309.
    doi: 10.1016/S0749-0739(17)30397-8pmc: PMC7134676pubmed: 8395325google scholar: lookup
  5. Balasuriya UB. Equine viral arteritis. Vet Clin Equine Pract 30:543–560.
    doi: 10.1016/j.cveq.2014.08.011pubmed: 25441113google scholar: lookup
  6. Timoney P, McCollum W. Equine viral arteritis: further characterization of the carrier state in stallions. J Reprod Fertil Suppl 56:3–11.
    pubmed: 20681110
  7. McCollum W, Timoney P, Lee J Jr, Habacker P, Balasuriya U, MacLachlan N. Features of an outbreak of equine viral arteritis on a breeding farm associated with abortion and fatal interstitial pneumonia in neonatal foals. Proc Conf Equine Infect Dis, VIII p 559–560.
  8. McCollum W, Timoney P, Tengelsen L. Clinical, virological and serological responses of donkeys to intranasal inoculation with the KY-84 strain of equine arteritis virus. J Comp Pathol 112:207–211.
    doi: 10.1016/S0021-9975(05)80062-3pubmed: 7769149google scholar: lookup
  9. Vaala W, Hamir A, Dubovi E, Timoney P, Ruiz B. Fatal, congenitally acquired infection with equine arteritis virus in a neonatal thoroughbred. Equine Vet J 24:155–158.
    doi: 10.1111/j.2042-3306.1992.tb02803.xpubmed: 1316264google scholar: lookup
  10. Timoney P, McCollum W. Equine viral arteritis–epidemiology and control. J Equine Vet Sci 8:54–59.
    doi: 10.1016/S0737-0806(88)80112-6google scholar: lookup
  11. McCollum W, Timoney P. The pathogenic qualities of the 1984 strain of equine arteritis virus. Proc Grayson Found Int Conf Thoroughbred Breeders Org, Ireland p 34–84.
  12. Bryans J, Doll E, Jones T. The lesions of equine viral arteritis. Cornell Vet 47:52.
    pubmed: 13397179
  13. Timoney PJ, McCollum WH. Equine viral arteritis. Can Vet J 28:693.
    pmc: PMC1680490pubmed: 17422919
  14. Bryans J, Doll E, Knappenberger R. An outbreak of abortion caused by the equine arteritis virus. Cornell Vet 47:69.
    pubmed: 13397180
  15. Bryans J, Crowe M, Doll E, McCollum W. Isolation of a filterable agent causing arteritis of horses and abortion by mares; its differentiation from the equine abortion (influenza) virus. Cornell Vet 47:3.
    pubmed: 13397177
  16. Timoney P, McCollum W, Murphy T, Roberts A, Willard J, Carswell G. The carrier state in equine arteritis virus infection in the stallion with specific emphasis on the venereal mode of virus transmission. J Reprod Fertil Suppl 35:95–102.
    pubmed: 2824772
  17. Glaser A, De Vries A, Rottier P, Horzinek M, Colenbrander B. Equine arteritis virus: a review of clinical features and management aspects. Vet Q 18:95–99.
    doi: 10.1080/01652176.1996.9694625pubmed: 8903141google scholar: lookup
  18. McCollum W, Little T, Timoney P, Swerczek T. Resistance of castrated male horses to attempted establishment of the carrier state with equine arteritis virus. J Comp Pathol 111:383–388.
    doi: 10.1016/S0021-9975(05)80096-9pubmed: 7884055google scholar: lookup
  19. Little T, Holyoak G, McCollum W, Timoney P. Output of equine arteritis virus from persistently infected stallions is testosterone-dependent. Proc Int Conf Equine Infect Dis. VI p 225–229.
  20. Timoney P, McCollum W, Roberts A, Murphy T. Demonstration of the carrier state in naturally acquired equine arteritis virus infection in the stallion. Res Vet Sci 41:279–280.
    doi: 10.1016/S0034-5288(18)30616-7pubmed: 3022363google scholar: lookup
  21. Kuhn JH, Lauck M, Bailey AL, Shchetinin AM, Vishnevskaya TV, Bào Y, Ng TFF, LeBreton M, Schneider BS, Gillis A, Tamoufe U, Diffo JLD, Takuo JM, Kondov NO, Coffey LL, Wolfe ND, Delwart E, Clawson AN, Postnikova E, Bollinger L, Lackemeyer MG, Radoshitzky SR, Palacios G, Wada J, Shevtsova ZV, Jahrling PB, Lapin BA, Deriabin PG, Dunowska M, Alkhovsky SV, Rogers J, Friedrich TC, O'Connor DH, Goldberg TL. Reorganization and expansion of the nidoviral family Arteriviridae. Arch Virol 161:755–768.
    doi: 10.1007/s00705-015-2672-zpmc: PMC5573231pubmed: 26608064google scholar: lookup
  22. Plagemann PG, Moennig V. Lactate dehydrogenase-elevating virus, equine arteritis virus, and simian hemorrhagic fever virus: a new group of positive-strand RNA viruses. Adv Virus Res 41:99–192.
    doi: 10.1016/S0065-3527(08)60036-6pmc: PMC7131515pubmed: 1315480google scholar: lookup
  23. Balasuriya UB, Go YY, MacLachlan NJ. Equine arteritis virus. Vet Microbiol 167:93–122.
    doi: 10.1016/j.vetmic.2013.06.015pmc: PMC7126873pubmed: 23891306google scholar: lookup
  24. Snijder EJ, Kikkert M, Fang Y. Arterivirus molecular biology and pathogenesis. J Gen Virol 94:2141–2163.
    doi: 10.1099/vir.0.056341-0pubmed: 23939974google scholar: lookup
  25. De Vries A, Chirnside E, Horzinek M, Rottier P. Structural proteins of equine arteritis virus. J Virol 66:6294–6303.
    pmc: PMC240121pubmed: 1328669
  26. Snijder EJ, Van Tol H, Pedersen KW, Raamsman MJ, de Vries AA. Identification of a novel structural protein of arteriviruses. J Virol 73:6335–6345.
    pmc: PMC112712pubmed: 10400725
  27. Balasuriya UB, MacLachlan NJ, De Vries AA, Rossitto PV, Rottier PJ. Identification of a neutralization site in the major envelope glycoprotein (G L) of equine arteritis virus. Virology 207:518–527.
    doi: 10.1006/viro.1995.1112pubmed: 7533965google scholar: lookup
  28. Balasuriya UB, Dobbe JC, Heidner HW, Smalley VL, Navarrette A, Snijder EJ, MacLachlan NJ. Characterization of the neutralization determinants of equine arteritis virus using recombinant chimeric viruses and site-specific mutagenesis of an infectious cDNA clone. Virology 321:235–246.
    doi: 10.1016/j.virol.2003.12.015pubmed: 15051384google scholar: lookup
  29. Balasuriya UB, Patton JF, Rossitto PV, Timoney PJ, McCollum WH, Maclachlan NJ. Neutralization determinants of laboratory strains and field isolates of equine arteritis virus: identification of four neutralization sites in the amino-terminal ectodomain of the GLenvelope glycoprotein. Virology 232:114–128.
    doi: 10.1006/viro.1997.8551pubmed: 9185595google scholar: lookup
  30. Zhang J, Timoney PJ, Shuck KM, Seoul G, Go YY, Lu Z, Powell DG, Meade BJ, Balasuriya UBR. Molecular epidemiology and genetic characterization of equine arteritis virus isolates associated with the 2006–2007 multi-state disease occurrence in the USA. J Gen Virol 91:2286–2301.
    doi: 10.1099/vir.0.019737-0pubmed: 20444993google scholar: lookup
  31. Balasuriya UB, MacLachlan NJ. The immune response to equine arteritis virus: potential lessons for other arteriviruses. Vet Immunol Immunopathol 102:107–129.
    doi: 10.1016/j.vetimm.2004.09.003pubmed: 15507299google scholar: lookup
  32. Hullinger PJ, Gardner IA, Hietala SK, Ferraro GL, MacLachlan NJ. Seroprevalence of antibodies against equine arteritis virus in horses residing in the United States and imported horses. J Am Vet Med Assoc 219:946–949.
    doi: 10.2460/javma.2001.219.946pubmed: 11601790google scholar: lookup
  33. Zhang J, Miszczak F, Pronost S, Fortier C, Balasuriya U, Zientara S, Fortier G, Timoney P. Genetic variation and phylogenetic analysis of 22 French isolates of equine arteritis virus. Arch Virol 152:1977–1994.
    doi: 10.1007/s00705-007-1040-zpubmed: 17680321google scholar: lookup
  34. Stadejek T, Björklund H, Bascuñana CR, Ciabatti IM, Scicluna MT, Amaddeo D, McCollum WH, Autorino GL, Timoney PJ, Paton DJ, Klingeborn B, Belák S. Genetic diversity of equine arteritis virus. J Gen Virol 80:691–699.
    doi: 10.1099/0022-1317-80-3-691pubmed: 10092009google scholar: lookup
  35. Hedges JF, Balasuriya UB, Timoney PJ, McCollum WH, MacLachlan NJ. Genetic variation in open reading frame 2 of field isolates and laboratory strains of equine arteritis virus. Virus Res 42:41–52.
    doi: 10.1016/0168-1702(96)01294-4pmc: PMC7133956pubmed: 8806173google scholar: lookup
  36. Murphy T, McCollum W, Timoney P, Klingeborn B, Hyllseth B, Golnik W, Erasmus B. Genomic variability among globally distributed isolates of equine arteritis virus. Vet Microbiol 32:101–115.
    doi: 10.1016/0378-1135(92)90099-Fpubmed: 1332249google scholar: lookup
  37. Balasuriya UB, Timoney PJ, Mccollum WH, Maclachlan NJ. Phylogenetic analysis of open reading frame 5 of field isolates of equine arteritis virus and identification of conserved and nonconserved regions in the G L envelope glycoprotein. Virology 214:690–697.
    doi: 10.1006/viro.1995.0087pubmed: 8553578google scholar: lookup
  38. Mittelholzer C, Stadejek T, Johansson I, Baule C, Ciabatti I, Hannant D, Paton D, Autorino G, Nowotny N, Belak S. Extended phylogeny of equine arteritis virus: division into new subgroups. J Vet Med Ser B 53:55–58.
    doi: 10.1111/j.1439-0450.2006.00916.xpubmed: 16626399google scholar: lookup
  39. Steinhauer D, Holland J. Rapid evolution of RNA viruses. Annu Rev Microbiol 41:409–431.
    doi: 10.1146/annurev.mi.41.100187.002205pubmed: 3318675google scholar: lookup
  40. Domingo E. Rapid evolution of viral RNA genomes. J Nutr 127:958S–961S.
    doi: 10.1093/jn/127.5.958Spubmed: 9164273google scholar: lookup
  41. Moya A, Elena SF, Bracho A, Miralles R, Barrio E. The evolution of RNA viruses: a population genetics view. Proc Natl Acad Sci U S A 97:6967–6973.
    doi: 10.1073/pnas.97.13.6967pmc: PMC34371pubmed: 10860958google scholar: lookup
  42. Lauring AS, Andino R. Quasispecies theory and the behavior of RNA viruses. PLoS Pathog 6:e1001005.
    doi: 10.1371/journal.ppat.1001005pmc: PMC2908548pubmed: 20661479google scholar: lookup
  43. Domingo E, Sheldon J, Perales C. Viral quasispecies evolution. Microbiol Mol Biol Rev 76:159–216.
    doi: 10.1128/MMBR.05023-11pmc: PMC3372249pubmed: 22688811google scholar: lookup
  44. Balasuriya UB, Snijder EJ, Van Dinten LC, Heidner HW, Wilson WD, Hedges JF, Hullinger PJ, MacLachlan NJ. Equine arteritis virus derived from an infectious cDNA clone is attenuated and genetically stable in infected stallions. Virology 260:201–208.
    doi: 10.1006/viro.1999.9817pubmed: 10405372google scholar: lookup
  45. Wright CF, Morelli MJ, Thébaud G, Knowles NJ, Herzyk P, Paton DJ, Haydon DT, King DP. Beyond the consensus: dissecting within-host viral population diversity of foot-and-mouth disease virus by using next-generation genome sequencing. J Virol 85:2266–2275.
    doi: 10.1128/JVI.01396-10pmc: PMC3067773pubmed: 21159860google scholar: lookup
  46. Poirier EZ, Vignuzzi M. Virus population dynamics during infection. Curr Opin Virol 23:82–87.
    doi: 10.1016/j.coviro.2017.03.013pubmed: 28456056google scholar: lookup
  47. Carossino M, Loynachan AT, Canisso IF, Cook RF, Campos JR, Nam B, Go YY, Squires EL, Troedsson MH, Swerczek T. Equine arteritis virus has specific tropism for stromal cells and CD8+ T and CD21+ B lymphocytes but not for glandular epithelium at the primary site of persistent infection in the stallion reproductive tract. J Virol 91:e00418-17.
    pmc: PMC5469258pubmed: 28424285
  48. Campos JR, Breheny P, Araujo RR, Troedsson MH, Squires EL, Timoney PJ, Balasuriya UB. Semen quality of stallions challenged with the Kentucky 84 strain of equine arteritis virus. Theriogenology 82:1068–1079.
    doi: 10.1016/j.theriogenology.2014.07.004pubmed: 25156969google scholar: lookup
  49. Muse SV, Gaut BS. A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. Mol Biol Evol 11:715–724.
    doi: 10.1093/oxfordjournals.molbev.a040152pubmed: 7968485google scholar: lookup
  50. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874.
    doi: 10.1093/molbev/msw054pmc: PMC8210823pubmed: 27004904google scholar: lookup
  51. Moncla LH, Zhong G, Nelson CW, Dinis JM, Mutschler J, Hughes AL, Watanabe T, Kawaoka Y, Friedrich TC. Selective bottlenecks shape evolutionary pathways taken during mammalian adaptation of a 1918-like avian influenza virus. Cell Host Microbe 19:169–180.
    doi: 10.1016/j.chom.2016.01.011pmc: PMC4761429pubmed: 26867176google scholar: lookup
  52. Go YY, Cook RF, Fulgêncio JQ, Campos JR, Henney P, Timoney PJ, Horohov DW, Balasuriya UB. Assessment of correlation between in vitro CD3+ T cell susceptibility to EAV infection and clinical outcome following experimental infection. Vet Microbiol 157:220–225.
    doi: 10.1016/j.vetmic.2011.11.031pubmed: 22177968google scholar: lookup
  53. Go YY, Bailey E, Timoney PJ, Shuck KM, Balasuriya UB. Evidence that in vitro susceptibility of CD3+ T lymphocytes to equine arteritis virus infection reflects genetic predisposition of naturally infected stallions to become carriers of the virus. J Virol 86:12407–12410.
    doi: 10.1128/JVI.01698-12pmc: PMC3486460pubmed: 22933293google scholar: lookup
  54. Moya A, Holmes EC, González-Candelas F. The population genetics and evolutionary epidemiology of RNA viruses. Nat Rev Microbiol 2:279–288.
    doi: 10.1038/nrmicro863pmc: PMC7096949pubmed: 15031727google scholar: lookup
  55. Elde NC. Poliovirus evolution: the strong, silent type. Cell Host Microbe 12:605–606.
    doi: 10.1016/j.chom.2012.11.002pmc: PMC3518375pubmed: 23159048google scholar: lookup
  56. Grubaugh ND, Andersen KG. Experimental evolution to study virus emergence. Cell 169:1–3.
    doi: 10.1016/j.cell.2017.03.018pubmed: 28340335google scholar: lookup
  57. Hedges JF, Balasuriya UB, Timoney PJ, McCollum WH, MacLachlan NJ. Genetic divergence with emergence of novel phenotypic variants of equine arteritis virus during persistent infection of stallions. J Virol 73:3672–3681.
    pmc: PMC104142pubmed: 10196259
  58. Palmer BA, Dimitrova Z, Skums P, Crosbie O, Kenny-Walsh E, Fanning LJ. Analysis of the evolution and structure of a complex intrahost viral population in chronic hepatitis C virus mapped by ultradeep pyrosequencing. J Virol 88:13709–13721.
    doi: 10.1128/JVI.01732-14pmc: PMC4248971pubmed: 25231312google scholar: lookup
  59. Vrancken B, Suchard MA, Lemey P. Accurate quantification of within-and between-host HBV evolutionary rates requires explicit transmission chain modelling. Virus Evol 3:vex028.
    doi: 10.1093/ve/vex028pmc: PMC5632516pubmed: 29026650google scholar: lookup
  60. Parameswaran P, Wang C, Trivedi SB, Eswarappa M, Montoya M, Balmaseda A, Harris E. Intrahost selection pressures drive rapid dengue virus microevolution in acute human infections. Cell Host Microbe 22:400–410.
    doi: 10.1016/j.chom.2017.08.003pmc: PMC5616187pubmed: 28910637google scholar: lookup
  61. Feder AF, Kline C, Polacino P, Cottrell M, Kashuba AD, Keele BF, Hu S-L, Petrov DA, Pennings PS, Ambrose Z. A spatio-temporal assessment of simian/human immunodeficiency virus (SHIV) evolution reveals a highly dynamic process within the host. PLoS Pathog 13:e1006358.
    doi: 10.1371/journal.ppat.1006358pmc: PMC5444849pubmed: 28542550google scholar: lookup
  62. Leonard AS, McClain MT, Smith GJ, Wentworth DE, Halpin RA, Lin X, Ransier A, Stockwell TB, Das SR, Gilbert AS. Deep sequencing of influenza a virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification. J Virol 90:11247–11258.
    doi: 10.1128/JVI.01657-16pmc: PMC5126380pubmed: 27707932google scholar: lookup
  63. Rola J, Socha W, Zmudzinski JF. Sequence analysis of ORFs 5, 6 and 7 of equine arteritis virus during persistent infection of the stallion–a 7-year study. Vet Microbiol 164:378–382.
    doi: 10.1016/j.vetmic.2013.02.011pubmed: 23490558google scholar: lookup
  64. Moncla LH, Florek NW, Friedrich TC. Influenza evolution: new insights into an old foe. Trends Microbiol 25:432–434.
    doi: 10.1016/j.tim.2017.04.003pubmed: 28478941google scholar: lookup
  65. Villarreal LP, Witzany G. Rethinking quasispecies theory: from fittest type to cooperative consortia. World J Biol Chem 4:79.
    doi: 10.4331/wjbc.v4.i4.79pmc: PMC3856310pubmed: 24340131google scholar: lookup
  66. OhAinle M, Balmaseda A, Macalalad AR, Tellez Y, Zody MC, Saborio S, Nunez A, Lennon NJ, Birren BW, Gordon A, Henn MR, Harris E. Dynamics of dengue disease severity determined by the interplay between viral genetics and serotype-specific immunity. Sci Transl Med 3:114ra128.
    doi: 10.1126/scitranslmed.3003084pmc: PMC4517192pubmed: 22190239google scholar: lookup
  67. Dudley DM, Newman CM, Lalli J, Stewart LM, Koenig MR, Weiler AM, Semler MR, Barry GL, Zarbock KR, Mohns MS, Breitbach ME, Schultz-Darken N, Peterson E, Newton W, Mohr EL, Capuano Iii S, Osorio JE, O'Connor SL, O'Connor DH, Friedrich TC, Aliota MT. Infection via mosquito bite alters Zika virus tissue tropism and replication kinetics in rhesus macaques. Nat Commun 8:2096.
    doi: 10.1038/s41467-017-02222-8pmc: PMC5727388pubmed: 29235456google scholar: lookup
  68. Xiao Y, Dolan PT, Goldstein EF, Li M, Farkov M, Brodsky L, Andino R. Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses. Nat Commun 8:375.
    doi: 10.1038/s41467-017-00354-5pmc: PMC5575128pubmed: 28851882google scholar: lookup
  69. Liu Y, Liu J, Du S, Shan C, Nie K, Zhang R, Li X-F, Zhang R, Wang T, Qin C-F, Wang P, Shi P-Y, Cheng G. Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature 545:482–486.
    doi: 10.1038/nature22365pmc: PMC5885636pubmed: 28514450google scholar: lookup
  70. Miszczak F, Shuck KM, Lu Z, Go YY, Zhang J, Sells S, Vabret A, Pronost S, Fortier G, Timoney PJ, Balasuriya UB. Evaluation of two magnetic-bead-based viral nucleic acid purification kits and three real-time reverse transcription-PCR reagent systems in two TaqMan assays for equine arteritis virus detection in semen. J Clin Microbiol 49:3694–3696.
    doi: 10.1128/JCM.01187-11pmc: PMC3187312pubmed: 21832018google scholar: lookup
  71. Culasso A, Baré P, Aloisi N, Monzani M, Corti M, Campos R. Intra-host evolution of multiple genotypes of hepatitis C virus in a chronically infected patient with HIV along a 13-year follow-up period. Virology 449:317–327.
    doi: 10.1016/j.virol.2013.11.034pubmed: 24418566google scholar: lookup
  72. Anderson JA, Ping L-H, Dibben O, Jabara CB, Arney L, Kincer L, Tang Y, Hobbs M, Hoffman I, Kazembe P, Jones CD, Borrow P, Fiscus S, Cohen MS, Swanstrom R. HIV-1 populations in semen arise through multiple mechanisms. PLoS Pathog 6:e1001053.
    doi: 10.1371/journal.ppat.1001053pmc: PMC2924360pubmed: 20808902google scholar: lookup
  73. Moncla LH, Weiler AM, Barry G, Weinfurter JT, Dinis JM, Charlier O, Lauck M, Bailey AL, Wahl-Jensen V, Nelson CW. Within-host evolution of simian arteriviruses in crab-eating macaques. J Virol 91:e02231-16.
    pmc: PMC5286893pubmed: 27974564
  74. Poon LLM, Song T, Rosenfeld R, Lin X, Rogers MB, Zhou B, Sebra R, Halpin RA, Guan Y, Twaddle A, DePasse JV, Stockwell TB, Wentworth DE, Holmes EC, Greenbaum B, Peiris JSM, Cowling BJ, Ghedin E. Quantifying influenza virus diversity and transmission in humans. Nat Genet 48:195–200.
    doi: 10.1038/ng.3479pmc: PMC4731279pubmed: 26727660google scholar: lookup
  75. Varble A, Albrecht RA, Backes S, Crumiller M, Bouvier NM, Sachs D, García-Sastre A, tenOever BR. Influenza A virus transmission bottlenecks are defined by infection route and recipient host. Cell Host Microbe 16:691–700.
    doi: 10.1016/j.chom.2014.09.020pmc: PMC4272616pubmed: 25456074google scholar: lookup
  76. Vasilakis N, Deardorff ER, Kenney JL, Rossi SL, Hanley KA, Weaver SC. Mosquitoes put the brake on arbovirus evolution: experimental evolution reveals slower mutation accumulation in mosquito than vertebrate cells. PLoS Pathog 5:e1000467.
    doi: 10.1371/journal.ppat.1000467pmc: PMC2685980pubmed: 19503824google scholar: lookup
  77. Go YY, Zhang J, Timoney PJ, Cook RF, Horohov DW, Balasuriya UB. Complex interactions between the major and minor envelope proteins of equine arteritis virus determine its tropism for equine CD3+ T lymphocytes and CD14+ monocytes. J Virol 84:4898–4911.
    doi: 10.1128/JVI.02743-09pmc: PMC2863813pubmed: 20219931google scholar: lookup
  78. Balasuriya UBR, Sarkar S, Carossino M, Go YY, Chelvarajan L, Cook RF, Loynachan AT, Timoney PJ, Bailey E. Host factors that contribute to equine arteritis virus persistence in the stallion: an update. J Equine Vet Sci 43:S11–S17.
    doi: 10.1016/j.jevs.2016.05.017google scholar: lookup
  79. Wang L, Valderramos SG, Wu A, Ouyang S, Li C, Brasil P, Bonaldo M, Coates T, Nielsen-Saines K, Jiang T, Aliyari R, Cheng G. From mosquitos to humans: genetic evolution of Zika virus. Cell Host Microbe 19:561–565.
    doi: 10.1016/j.chom.2016.04.006pmc: PMC5648540pubmed: 27091703google scholar: lookup
  80. Go YY, Bailey E, Cook DG, Coleman SJ, MacLeod JN, Chen K-C, Timoney PJ, Balasuriya UB. Genome-wide association study among four horse breeds identifies a common haplotype associated with in vitro CD3+ T cell susceptibility/resistance to equine arteritis virus infection. J Virol 85:13174–13184.
    doi: 10.1128/JVI.06068-11pmc: PMC3233183pubmed: 21994447google scholar: lookup
  81. Carossino M, Wagner B, Loynachan AT, Cook RF, Canisso IF, Chelvarajan L, Edwards CL, Nam B, Timoney JF, Timoney PJ. Equine arteritis virus elicits a mucosal antibody response in the reproductive tract of persistently infected stallions. Clin Vaccine Immunol 24:e00215-17.
    pmc: PMC5629664pubmed: 28814389
  82. Holyoak GR, Little T, McCollum W, Timoney P. Relationship between onset of puberty and establishment of persistent infection with equine arteritis virus in the experimentally infected colt. J Comp Pathol 109:29–46.
    doi: 10.1016/S0021-9975(08)80238-1pmc: PMC7130259pubmed: 8408779google scholar: lookup
  83. Grossman CJ. Regulation of the immune system by sex steroids. Endocr Rev 5:435–455.
    doi: 10.1210/edrv-5-3-435pubmed: 6381037google scholar: lookup
  84. Muehlenbein MP, Bribiescas RG. Testosterone mediated immune functions and male life histories. Am J Hum Biol 17:527–558.
    doi: 10.1002/ajhb.20419pubmed: 16136532google scholar: lookup
  85. Dejucq N, Jégou B. Viruses in the mammalian male genital tract and their effects on the reproductive system. Microbiol Mol Biol Rev 65:208–231.
    doi: 10.1128/MMBR.65.2.208-231.2001pmc: PMC99025pubmed: 11381100google scholar: lookup
  86. Rettew JA, Huet-Hudson YM, Marriott I. Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod 78:432–437.
    doi: 10.1095/biolreprod.107.063545pubmed: 18003947google scholar: lookup
  87. Balasuriya U, Carossino M, Timoney P. Equine viral arteritis: a respiratory and reproductive disease of significant economic importance to the equine industry. Equine Vet Ed .
    doi: 10.1111/eve.12672google scholar: lookup
  88. Neu SM, Timoney PJ, McCollum WH. Persistent infection of the reproductive tract in stallions experimentally infected with equine arteritis virus. Proc 5th Int Conf Equine Infect Dis The University Press of Kentucky, Lexington, Kentucky p 149–154.
  89. Balasuriya UBR, Carossino M. Reproductive effects of arteriviruses: equine arteritis virus and porcine reproductive and respiratory syndrome virus infections. Curr Opin Virol 27:57–70.
    doi: 10.1016/j.coviro.2017.11.005pubmed: 29172072google scholar: lookup
  90. National Research Council. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.
  91. Balasuriya UB, Snijder EJ, Heidner HW, Zhang J, Zevenhoven-Dobbe JC, Boone JD, McCollum WH, Timoney PJ, MacLachlan NJ. Development and characterization of an infectious cDNA clone of the virulent Bucyrus strain of Equine arteritis virus. J Gen Virol 88:918–924.
    doi: 10.1099/vir.0.82415-0pubmed: 17325365google scholar: lookup
  92. Delcher AL, Bratke KA, Powers EC, Salzberg SL. Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics 23:673–679.
    doi: 10.1093/bioinformatics/btm009pmc: PMC2387122pubmed: 17237039google scholar: lookup
  93. Guindon S, Dufayard J-F, Lefort V, Anisimova M, Hordijk W, Gascuel O. New algorithms and methods to estimate maximum likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 59:307–321.
    doi: 10.1093/sysbio/syq010pubmed: 20525638google scholar: lookup

Citations

This article has been cited 5 times.
  1. Spruill-Harrell B, Ponce-Flores A, Nnamani EI, Owen RD, Whitt MA, Jonsson CB. Purifying selection constrains the evolution of Juquitiba virus in wild Oligoryzomys nigripes communities. PLoS Pathog 2026 Jan;22(1):e1013839.
    doi: 10.1371/journal.ppat.1013839pubmed: 41557735google scholar: lookup
  2. Drolet BS, Reister-Hendricks L, Mayo C, Rodgers C, Molik DC, McVey DS. Increased Virulence of Culicoides Midge Cell-Derived Bluetongue Virus in IFNAR Mice. Viruses 2024 Sep 17;16(9).
    doi: 10.3390/v16091474pubmed: 39339950google scholar: lookup
  3. Wang X, Chen Y, Qi C, Li F, Zhang Y, Zhou J, Wu H, Zhang T, Qi A, Ouyang H, Xie Z, Pang D. Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles. Front Immunol 2024;15:1340332.
    doi: 10.3389/fimmu.2024.1340332pubmed: 38919631google scholar: lookup
  4. Cai H, Zhang H, Cheng H, Liu M, Wen S, Ren J. Progress in PRRSV Infection and Adaptive Immune Response Mechanisms. Viruses 2023 Jun 27;15(7).
    doi: 10.3390/v15071442pubmed: 37515130google scholar: lookup
  5. Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Cook RF, Timoney PJ, Balasuriya UBR. Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis. PLoS Pathog 2019 Jul;15(7):e1007950.
    doi: 10.1371/journal.ppat.1007950pubmed: 31356622google scholar: lookup
Subscribe to our newsletter
Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.