FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / J Virol / Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes a...
Journal of virology2018; 92(9); doi: 10.1128/JVI.00015-18

Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus.

Abstract: Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion.IMPORTANCE Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and is maintained despite induction of local inflammatory, humoral, and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first time, this study suggests complex interactions between eca-mir-128 and cellular elements at the site of EAV persistence and implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the reproductive tract during long-term persistence.
Copyright © 2018 American Society for Microbiology.
Get Full Text
Publication Date: 2018-04-13 PubMed ID: 29444949PubMed Central: PMC5899189DOI: 10.1128/JVI.00015-18Google 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 research article discusses a link between long-term persistence of equine arteritis virus (EAV) in the reproductive tract of stallions and two specific genetic factors: the downregulation of a microRNA (eca-mir-128) in seminal exosomes and the heightened expression of CXCL16 in the reproductive tract. The findings suggest that observations could be key in explaining EAV persistence and might provide the basis for future therapeutics.

Key Concepts

  • Equine arteritis virus (EAV) is a virus capable of establishing long-lasting infections in the reproductive tracts of stallions, shedding through their semen. This shed virus jeopardises global efforts to control the spread of EAV.
  • MicroRNAs (miRNAs) are small non-coding RNAs that play a significant role in controlling gene expression. They are often found within seminal exosomes (SEs), which are small vesicles excreted by cells.
  • This study has identified a specific miRNA, eca-mir-128, that is linked to the persistence of EAV. The research found that this miRNA is ‘downregulated’, or reduced in stallions with persistent EAV, suggesting it could be a contributing factor to the virus’s long-term presence.
  • CXCL16 is a chemokine, a type of protein involved in triggering immune responses. In this study, an increased expression of CXCL16 was associated with EAV persistence. Furthermore, CXCL16 is understood to be a target of eca-mir-128, the miRNA found to be downregulated in the seminal exosomes.

Implications and Future Perspectives

  • These findings imply that eca-mir-128 could be involved in regulating the CXCL16/CXCR6 axis in the reproductive tracts of persistently infected stallions.
  • However, the exact interaction and mechanisms by which eca-mir-128 influences this chemokine axis, and thereby the persistence of EAV, still need to be identified.
  • Understanding the role played by eca-mir-128 could help in the development of effective therapeutics that target the miRNA or its associated proteins to eliminate persistent infections.
  • The authors suggest that this study provides a starting point for a new line of research within the field of viral persistence in the reproductive tract.

Cite This Article

APA
Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Shuck KM, Timoney PJ, Cook RF, Balasuriya UBR. (2018). Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus. J Virol, 92(9). https://doi.org/10.1128/JVI.00015-18

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 92
Issue: 9

Researcher Affiliations

Carossino, Mariano
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Dini, Pouya
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
  • Department of Veterinary Imaging, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Kalbfleisch, Theodore S
  • Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, Kentucky, USA.
Loynachan, Alan T
  • University of Kentucky Veterinary Diagnostic Laboratory, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Canisso, Igor F
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
  • Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
Shuck, Kathleen M
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Timoney, Peter J
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Cook, R Frank
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Balasuriya, Udeni B R
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA ubalasuriya@uky.edu.

MeSH Terms

  • Animals
  • Arterivirus Infections / veterinary
  • Arterivirus Infections / virology
  • Chemokine CXCL16 / biosynthesis
  • Down-Regulation / genetics
  • Equartevirus / physiology
  • Exosomes / genetics
  • Genitalia, Male / metabolism
  • Genitalia, Male / virology
  • Horse Diseases / virology
  • Horses
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Receptors, CXCR6 / biosynthesis
  • Semen / cytology

References

This article includes 114 references
  1. Balasuriya U, MacLachlan NJ. Equine viral arteritis. 2013 p 169–181.
  2. Balasuriya UB, Go YY, MacLachlan NJ. Equine arteritis virus. Vet Microbiol 2013 167:93–122.
    doi: 10.1016/j.vetmic.2013.06.015pmc: PMC7126873pubmed: 23891306google scholar: lookup
  3. Balasuriya UBR, Carossino M, Timoney PJ. Equine viral arteritis: a respiratory and reproductive disease of significant economic importance to the equine industry. Equine Vet Educ 2016 Nov 10.
    doi: 10.1111/eve.12672google scholar: lookup
  4. Timoney PJ. The increasing significance of international trade in equids and its influence on the spread of infectious diseases. Ann N Y Acad Sci 2000 916:55–60.
    doi: 10.1111/j.1749-6632.2000.tb05274.xpubmed: 11193671google scholar: lookup
  5. Timoney PJ. Factors influencing the international spread of equine diseases. Vet Clin North Am Equine Pract 2000 16:537–551.
    doi: 10.1016/S0749-0739(17)30094-9pubmed: 11219348google scholar: lookup
  6. Timoney PJ, McCollum WH. Equine viral arteritis: epidemiology and control. J Equine Vet Sci 1988 8:54–59.
    doi: 10.1016/S0737-0806(88)80112-6google scholar: lookup
  7. Timoney PJ, McCollum WH. Equine viral arteritis. Vet Clin North Am Equine Pract 1993 9:295–309.
    doi: 10.1016/S0749-0739(17)30397-8pmc: PMC7134676pubmed: 8395325google scholar: lookup
  8. Cavanagh D. Nidovirales: a new order comprising Coronaviridae and Arteriviridae. Arch Virol 1997 142:629–633.
    pubmed: 9349308
  9. Timoney PJ, McCollum WH. Equine viral arteritis: further characterization of the carrier state in stallions. J Reprod Fertil Suppl 2000 56:3–11.
    pubmed: 20681110
  10. Reference deleted.
  11. Timoney PJ, McCollum WH, Murphy TW, Roberts AW, Willard JG, Carswell GD. 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 1987 35:95–102.
    pubmed: 2824772
  12. Balasuriya U. Equine viral arteritis. Vet Clin North Am Equine Pract 2014 30:543–560.
    doi: 10.1016/j.cveq.2014.08.011pubmed: 25441113google scholar: lookup
  13. 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 2007 88:918–924.
    doi: 10.1099/vir.0.82415-0pubmed: 17325365google scholar: lookup
  14. 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 1999 260:201–208.
    doi: 10.1006/viro.1999.9817pubmed: 10405372google scholar: lookup
  15. Go YY, Cook RF, Fulgencio 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 2012 157:220–225.
    doi: 10.1016/j.vetmic.2011.11.031pubmed: 22177968google scholar: lookup
  16. MacLachlan NJ, Balasuriya UB, Rossitto PV, Hullinger PA, Patton JF, Wilson WD. Fatal experimental equine arteritis virus infection of a pregnant mare: immunohistochemical staining of viral antigens. J Vet Diagn Invest 1996 8:367–374.
    doi: 10.1177/104063879600800316pubmed: 8844583google scholar: lookup
  17. McCollum WH, Timoney PJ, Tengelsen LA. Clinical, virological and serological responses of donkeys to intranasal inoculation with the KY-84 strain of equine arteritis virus. J Comp Pathol 1995 112:207–211.
    doi: 10.1016/S0021-9975(05)80062-3pubmed: 7769149google scholar: lookup
  18. Vairo S, Vandekerckhove A, Steukers L, Glorieux S, Van den Broeck W, Nauwynck H. Clinical and virological outcome of an infection with the Belgian equine arteritis virus strain 08P178. Vet Microbiol 2012 157:333–344.
    doi: 10.1016/j.vetmic.2012.01.014pubmed: 22306037google scholar: lookup
  19. 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 2014 82:1068–1079.
    doi: 10.1016/j.theriogenology.2014.07.004pubmed: 25156969google scholar: lookup
  20. Vaala WE, Hamir AN, Dubovi EJ, Timoney PJ, Ruiz B. Fatal, congenitally acquired infection with equine arteritis virus in a neonatal thoroughbred. Equine Vet J 1992 24:155–158.
    doi: 10.1111/j.2042-3306.1992.tb02803.xpubmed: 1316264google scholar: lookup
  21. 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 2016 43:S11–S17.
    doi: 10.1016/j.jevs.2016.05.017google scholar: lookup
  22. Reference deleted.
  23. Timoney PJ, McCollum WH, Roberts AW, Murphy TW. Demonstration of the carrier state in naturally acquired equine arteritis virus infection in the stallion. Res Vet Sci 1986 41:279–280.
    pubmed: 3022363
  24. Reference deleted.
  25. McCollum WH, Little TV, Timoney PJ, Swerczek TW. Resistance of castrated male horses to attempted establishment of the carrier state with equine arteritis virus. J Comp Pathol 1994 111:383–388.
    doi: 10.1016/S0021-9975(05)80096-9pubmed: 7884055google scholar: lookup
  26. Carossino M, Loynachan AT, Canisso IF, Campos JR, Nam B, Go YY, Squires EL, Troedsson MHT, Cook RF, Swerczek T, Del Piero F, Bailey E, Timoney PJ, Balasuriya UBR. Equine arteritis virus has specific tropism for stromal cells and CD8+ T and CD21+ B lymphocytes but not glandular epithelium at the primary site of persistent infection in the stallion reproductive tract. J Virol 2017 91:e00418-.
    doi: 10.1128/JVI.00418-17pmc: PMC5469258pubmed: 28424285google scholar: lookup
  27. Carossino M, Wagner B, Loynachan AT, Cook RF, Canisso IF, Chelvarajan L, Edwards CL, Nam B, Timoney JF, Timoney PJ, Balasuriya UBR. Equine arteritis virus elicits a mucosal antibody response in the reproductive tract of persistently infected stallions. Clin Vaccine Immunol 2017 24:e00215-.
    doi: 10.1128/CVI.00215-17pmc: PMC5629664pubmed: 28814389google scholar: lookup
  28. Balasuriya UB, Carossino M. Reproductive effects of arteriviruses: equine arteritis virus and porcine reproductive and respiratory syndrome virus infections. Curr Opin Virol 2017 27:57–70.
    doi: 10.1016/j.coviro.2017.11.005pubmed: 29172072google scholar: lookup
  29. Go YY, Bailey E, Cook DG, Coleman SJ, Macleod JN, Chen KC, 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 2011 85:13174–13184.
    doi: 10.1128/JVI.06068-11pmc: PMC3233183pubmed: 21994447google scholar: lookup
  30. 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 2012 86:12407–12410.
    doi: 10.1128/JVI.01698-12pmc: PMC3486460pubmed: 22933293google scholar: lookup
  31. Sarkar S, Bailey E, Go YY, Cook RF, Kalbfleisch T, Eberth J, Chelvarajan RL, Shuck KM, Artiushin S, Timoney PJ, Balasuriya UB. Allelic variation in CXCL16 determines CD3+ T lymphocyte susceptibility to equine arteritis virus infection and establishment of long-term carrier state in the stallion. PLoS Genet 2016 12:e1006467.
    doi: 10.1371/journal.pgen.1006467pmc: PMC5145142pubmed: 27930647google scholar: lookup
  32. Jasko DJ. Evaluation of stallion semen. Vet Clin North Am Equine Pract 1992 8:129–148.
    doi: 10.1016/S0749-0739(17)30471-6pubmed: 1576546google scholar: lookup
  33. Aumüller G, Seitz J. Protein secretion and secretory processes in male accessory sex glands. Int Rev Cytol 1990 121:127–231.
    doi: 10.1016/S0074-7696(08)60660-9pubmed: 2190945google scholar: lookup
  34. Vojtech L, Woo S, Hughes S, Levy C, Ballweber L, Sauteraud RP, Strobl J, Westerberg K, Gottardo R, Tewari M, Hladik F. Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res 2014 42:7290–7304.
    doi: 10.1093/nar/gku347pmc: PMC4066774pubmed: 24838567google scholar: lookup
  35. Owen DH, Katz DF. A review of the physical and chemical properties of human semen and the formulation of a semen simulant. J Androl 2005 26:459–469.
    doi: 10.2164/jandrol.04104pubmed: 15955884google scholar: lookup
  36. Rodríguez-Martínez H, Kvist U, Saravia F, Wallgren M, Johannisson A, Sanz L, Pena FJ, Martinez EA, Roca J, Vazquez JM, Calvete JJ. The physiological roles of the boar ejaculate. Soc Reprod Fertil Suppl 2009 66:1–21.
    pubmed: 19848263
  37. Juyena NS, Stelletta C. Seminal plasma: an essential attribute to spermatozoa. J Androl 2012 33:536–551.
    doi: 10.2164/jandrol.110.012583pubmed: 22016346google scholar: lookup
  38. Larson BL, Salisbury GW. The proteins of bovine seminal plasma. I. Preliminary and electrophoretic studies. J Biol Chem 1954 206:741–749.
    pubmed: 13143036
  39. Kareskoski M, Katila T. Components of stallion seminal plasma and the effects of seminal plasma on sperm longevity. Anim Reprod Sci 2008 107:249–256.
    doi: 10.1016/j.anireprosci.2008.04.013pubmed: 18556156google scholar: lookup
  40. Caballero I, Parrilla I, Alminana C, del Olmo D, Roca J, Martinez EA, Vazquez JM. Seminal plasma proteins as modulators of the sperm function and their application in sperm biotechnologies. Reprod Domest Anim 2012 47(Suppl 3):S12–S21.
    doi: 10.1111/j.1439-0531.2012.02028.xpubmed: 22681294google scholar: lookup
  41. Aalberts M, Stout TA, Stoorvogel W. Prostasomes: extracellular vesicles from the prostate. Reproduction 2014 147:R1–R14.
    doi: 10.1530/REP-13-0358pubmed: 24149515google scholar: lookup
  42. Lazarevic M, Skibinski G, Kelly RW, James K. Immunomodulatory effects of extracellular secretory vesicles isolated from bovine semen. Vet Immunol Immunopathol 1995 44:237–250.
    doi: 10.1016/0165-2427(94)05320-Rpubmed: 7747404google scholar: lookup
  43. Madison MN, Roller RJ, Okeoma CM. Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology 2014 11:102.
    doi: 10.1186/s12977-014-0102-zpmc: PMC4245725pubmed: 25407601google scholar: lookup
  44. Piehl LL, Fischman ML, Hellman U, Cisale H, Miranda PV. Boar seminal plasma exosomes: effect on sperm function and protein identification by sequencing. Theriogenology 2013 79:1071–1082.
    doi: 10.1016/j.theriogenology.2013.01.028pubmed: 23489476google scholar: lookup
  45. Poliakov A, Spilman M, Dokland T, Amling CL, Mobley JA. Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate 2009 69:159–167.
    doi: 10.1002/pros.20860pubmed: 18819103google scholar: lookup
  46. Arienti G, Carlini E, De Cosmo AM, Di Profio P, Palmerini CA. Prostasome-like particles in stallion semen. Biol Reprod 1998 59:309–313.
    doi: 10.1095/biolreprod59.2.309pubmed: 9687300google scholar: lookup
  47. Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014 30:255–289.
    doi: 10.1146/annurev-cellbio-101512-122326pubmed: 25288114google scholar: lookup
  48. Kelly RW, Holland P, Skibinski G, Harrison C, McMillan L, Hargreave T, James K. Extracellular organelles (prostasomes) are immunosuppressive components of human semen. Clin Exp Immunol 1991 86:550–556.
    doi: 10.1111/j.1365-2249.1991.tb02968.xpmc: PMC1554200pubmed: 1747961google scholar: lookup
  49. Robertson SA, Guerin LR, Bromfield JJ, Branson KM, Ahlstrom AC, Care AS. Seminal fluid drives expansion of the CD4+CD25+ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod 2009 80:1036–1045.
    doi: 10.1095/biolreprod.108.074658pmc: PMC2849830pubmed: 19164169google scholar: lookup
  50. Madison MN, Okeoma CM. Exosomes: implications in HIV-1 pathogenesis. Viruses 2015 7:4093–4118.
    doi: 10.3390/v7072810pmc: PMC4517139pubmed: 26205405google scholar: lookup
  51. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007 9:654–659.
    doi: 10.1038/ncb1596pubmed: 17486113google scholar: lookup
  52. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004 116:281–297.
    doi: 10.1016/S0092-8674(04)00045-5pubmed: 14744438google scholar: lookup
  53. Fowler L, Saksena NK. Micro-RNA: new players in HIV-pathogenesis, diagnosis, prognosis and antiviral therapy. AIDS Rev 2013 15:3–14.
    pubmed: 23449224
  54. Verma P, Pandey RK, Prajapati P, Prajapati VK. Circulating microRNAs: potential and emerging biomarkers for diagnosis of human infectious diseases. Front Microbiol 2016 7:1274.
    doi: 10.3389/fmicb.2016.01274pmc: PMC4983550pubmed: 27574520google scholar: lookup
  55. Fiorino S, Bacchi-Reggiani ML, Visani M, Acquaviva G, Fornelli A, Masetti M, Tura A, Grizzi F, Zanello M, Mastrangelo L, Lombardi R, Di Tommaso L, Bondi A, Sabbatani S, Domanico A, Fabbri C, Leandri P, Pession A, Jovine E, de Biase D. MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma. World J Gastroenterol 2016 22:3907–3936.
    doi: 10.3748/wjg.v22.i15.3907pmc: PMC4823242pubmed: 27099435google scholar: lookup
  56. Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol 2016 231:25–30.
    doi: 10.1002/jcp.25056pmc: PMC8776330pubmed: 26031493google scholar: lookup
  57. Paziewska A, Mikula M, Dabrowska M, Kulecka M, Goryca K, Antoniewicz A, Dobruch J, Borowka A, Rutkowski P, Ostrowski J. Candidate diagnostic miRNAs that can detect cancer in prostate biopsy. Prostate 2017 Dec 11.
    doi: 10.1002/pros.23427pubmed: 29226351google scholar: lookup
  58. He Y, Deng F, Yang S, Wang D, Chen X, Zhong S, Zhao J, Tang J. Exosomal microRNA: a novel biomarker for breast cancer. Biomark Med 2017.
    doi: 10.2217/bmm-2017-0305pubmed: 29151358google scholar: lookup
  59. Kim MC, Lee SW, Ryu DY, Cui FJ, Bhak J, Kim Y. Identification and characterization of microRNAs in normal equine tissues by next generation sequencing. PLoS One 2014 9:e93662.
    doi: 10.1371/journal.pone.0093662pmc: PMC3973549pubmed: 24695583google scholar: lookup
  60. Desjardin C, Vaiman A, Mata X, Legendre R, Laubier J, Kennedy SP, Laloe D, Barrey E, Jacques C, Cribiu EP, Schibler L. Next-generation sequencing identifies equine cartilage and subchondral bone miRNAs and suggests their involvement in osteochondrosis physiopathology. BMC Genomics 2014 15:798.
    doi: 10.1186/1471-2164-15-798pmc: PMC4190437pubmed: 25227120google scholar: lookup
  61. da Silveira JC, Veeramachaneni DN, Winger QA, Carnevale EM, Bouma GJ. Cell-secreted vesicles in equine ovarian follicular fluid contain miRNAs and proteins: a possible new form of cell communication within the ovarian follicle. Biol Reprod 2012 86:71.
    doi: 10.1095/biolreprod.111.093252pubmed: 22116803google scholar: lookup
  62. da Silveira JC, Carnevale EM, Winger QA, Bouma GJ. Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation in the mare. Reprod Biol Endocrinol 2014 12:44.
    doi: 10.1186/1477-7827-12-44pmc: PMC4045866pubmed: 24884710google scholar: lookup
  63. Rout ED, Webb TL, Laurence HM, Long L, Olver CS. Transferrin receptor expression in serum exosomes as a marker of regenerative anaemia in the horse. Equine Vet J 2015 47:101–106.
    doi: 10.1111/evj.12235pubmed: 24708277google scholar: lookup
  64. Aalberts M, Sostaric E, Wubbolts R, Wauben MW, Nolte-'t Hoen EN, Gadella BM, Stout TA, Stoorvogel W. Spermatozoa recruit prostasomes in response to capacitation induction. Biochim Biophys Acta 2013 1834:2326–2335.
    doi: 10.1016/j.bbapap.2012.08.008pubmed: 22940639google scholar: lookup
  65. Kelly RW. Immunosuppressive mechanisms in semen: implications for contraception. Hum Reprod 1995 10:1686–1693.
    doi: 10.1093/oxfordjournals.humrep.a136156pubmed: 8582962google scholar: lookup
  66. Sullivan R, Saez F. Epididymosomes, prostasomes, and liposomes: their roles in mammalian male reproductive physiology. Reproduction 2013 146:R21–R35.
    doi: 10.1530/REP-13-0058pubmed: 23613619google scholar: lookup
  67. Tarazona R, Delgado E, Guarnizo MC, Roncero RG, Morgado S, Sanchez-Correa B, Gordillo JJ, Dejulian J, Casado JG. Human prostasomes express CD48 and interfere with NK cell function. Immunobiology 2011 216:41–46.
    doi: 10.1016/j.imbio.2010.03.002pubmed: 20382443google scholar: lookup
  68. Skibinski G, Kelly RW, Harkiss D, James K. Immunosuppression by human seminal plasma—extracellular organelles (prostasomes) modulate activity of phagocytic cells. Am J Reprod Immunol 1992 28:97–103.
    doi: 10.1111/j.1600-0897.1992.tb00767.xpubmed: 1337434google scholar: lookup
  69. Carissimi C, Carucci N, Colombo T, Piconese S, Azzalin G, Cipolletta E, Citarella F, Barnaba V, Macino G, Fulci V. miR-21 is a negative modulator of T-cell activation. Biochimie 2014 107(Part B):319–326.
    pubmed: 25304039
  70. Tsukerman P, Stern-Ginossar N, Gur C, Glasner A, Nachmani D, Bauman Y, Yamin R, Vitenshtein A, Stanietsky N, Bar-Mag T, Lankry D, Mandelboim O. MiR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells. Cancer Res 2012 72:5463–5472.
    doi: 10.1158/0008-5472.CAN-11-2671pubmed: 22915757google scholar: lookup
  71. Swaminathan S, Suzuki K, Seddiki N, Kaplan W, Cowley MJ, Hood CL, Clancy JL, Murray DD, Mendez C, Gelgor L, Anderson B, Roth N, Cooper DA, Kelleher AD. Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters IL-10 expression. J Immunol 2012 188:6238–6246.
    doi: 10.4049/jimmunol.1101196pubmed: 22586040google scholar: lookup
  72. Wells AC, Daniels KA, Angelou CC, Fagerberg E, Burnside AS, Markstein M, Alfandari D, Welsh RM, Pobezinskaya EL, Pobezinsky LA. Modulation of let-7 miRNAs controls the differentiation of effector CD8 T cells. Elife 2017 6:e26398.
    doi: 10.7554/eLife.26398pmc: PMC5550279pubmed: 28737488google scholar: lookup
  73. Kumar M, Sahu SK, Kumar R, Subuddhi A, Maji RK, Jana K, Gupta P, Raffetseder J, Lerm M, Ghosh Z, van Loo G, Beyaert R, Gupta UD, Kundu M, Basu J. MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-kappaB pathway. Cell Host Microbe 2015 17:345–356.
    doi: 10.1016/j.chom.2015.01.007pubmed: 25683052google scholar: lookup
  74. Podshivalova K, Salomon DR. MicroRNA regulation of T-lymphocyte immunity: modulation of molecular networks responsible for T-cell activation, differentiation, and development. Crit Rev Immunol 2013 33:435–476.
    doi: 10.1615/CritRevImmunol.2013006858pmc: PMC4185288pubmed: 24099302google scholar: lookup
  75. Lee S, Hwang S, Yu HJ, Oh D, Choi YJ, Kim MC, Kim Y, Ryu DY. Expression of microRNAs in horse plasma and their characteristic nucleotide composition. PLoS One 2016 11:e0146374.
    doi: 10.1371/journal.pone.0146374pmc: PMC4711666pubmed: 26731407google scholar: lookup
  76. Cowled C, Foo CH, Deffrasnes C, Rootes CL, Williams DT, Middleton D, Wang LF, Bean AGD, Stewart CR. Circulating microRNA profiles of Hendra virus infection in horses. Sci Rep 2017 7:7431.
    doi: 10.1038/s41598-017-06939-wpmc: PMC5547158pubmed: 28785041google scholar: lookup
  77. Ludwig N, Leidinger P, Becker K, Backes C, Fehlmann T, Pallasch C, Rheinheimer S, Meder B, Stahler C, Meese E, Keller A. Distribution of miRNA expression across human tissues. Nucleic Acids Res 2016 44:3865–3877.
    doi: 10.1093/nar/gkw116pmc: PMC4856985pubmed: 26921406google scholar: lookup
  78. Parkinson NJ, Buechner-Maxwell VA, Witonsky SG, Pleasant RS, Werre SR, Ahmed SA. Characterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using next-generation sequencing. PLoS One 2017 12:e0177664.
    doi: 10.1371/journal.pone.0177664pmc: PMC5446123pubmed: 28552958google scholar: lookup
  79. Dini P, Loux SC, Scoggin KE, Esteller-Vico A, Squires EL, Troedsson MHT, Daels P, Ball BA. Identification of reference genes for analysis of microRNA expression patterns in equine chorioallantoic membrane and serum. Mol Biotechnol 2018 60:62–73.
    doi: 10.1007/s12033-017-0047-2pubmed: 29197992google scholar: lookup
  80. McGivney BA, Griffin ME, Gough KF, McGivney CL, Browne JA, Hill EW, Katz LM. Evaluation of microRNA expression in plasma and skeletal muscle of thoroughbred racehorses in training. BMC Vet Res 2017 13:347.
    doi: 10.1186/s12917-017-1277-zpmc: PMC5700565pubmed: 29166903google scholar: lookup
  81. Li M, Fu W, Wo L, Shu X, Liu F, Li C. miR-128 and its target genes in tumorigenesis and metastasis. Exp Cell Res 2013 319:3059–3064.
    doi: 10.1016/j.yexcr.2013.07.031pubmed: 23958464google scholar: lookup
  82. Pacholewska A, Kraft MF, Gerber V, Jagannathan V. Differential expression of serum microRNAs supports CD4(+) T cell differentiation into Th2/Th17 cells in severe equine asthma. Genes (Basel) 2017 8(12):E383.
    doi: 10.3390/genes8120383pmc: PMC5748701pubmed: 29231896google scholar: lookup
  83. Nguyen MA, Karunakaran D, Geoffrion M, Cheng HS, Tandoc K, Perisic Matic L, Hedin U, Maegdefessel L, Fish JE, Rayner KJ. Extracellular vesicles secreted by atherogenic macrophages transfer microRNA to inhibit cell migration. Arterioscler Thromb Vasc Biol 2017 Sep 7.
    doi: 10.1161/ATVBAHA.117.309795pmc: PMC5884694pubmed: 28882869google scholar: lookup
  84. Geekiyanage H, Galanis E. MiR-31 and miR-128 regulates poliovirus receptor-related 4 mediated measles virus infectivity in tumors. Mol Oncol 2016 10:1387–1403.
    doi: 10.1016/j.molonc.2016.07.007pmc: PMC5100694pubmed: 27507538google scholar: lookup
  85. Eletto D, Russo G, Passiatore G, Del Valle L, Giordano A, Khalili K, Gualco E, Peruzzi F. Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a. J Cell Physiol 2008 216:764–770.
    doi: 10.1002/jcp.21452pmc: PMC2662126pubmed: 18381601google scholar: lookup
  86. Sarkar S, Chelvarajan L, Go YY, Cook F, Artiushin S, Mondal S, Anderson K, Eberth J, Timoney PJ, Kalbfleisch TS, Bailey E, Balasuriya UB. Equine arteritis virus uses equine CXCL16 as an entry receptor. J Virol 2016 90:3366–3384.
    doi: 10.1128/JVI.02455-15pmc: PMC4794689pubmed: 26764004google scholar: lookup
  87. Pillai RS. MicroRNA function: multiple mechanisms for a tiny RNA?. RNA 2005 11:1753–1761.
    doi: 10.1261/rna.2248605pmc: PMC1370863pubmed: 16314451google scholar: lookup
  88. Wang X. Composition of seed sequence is a major determinant of microRNA targeting patterns. Bioinformatics 2014 30:1377–1383.
    doi: 10.1093/bioinformatics/btu045pmc: PMC4016705pubmed: 24470575google scholar: lookup
  89. Ravon M, Berrera M, Ebeling M, Certa U. Single base mismatches in the mRNA target site allow specific seed region-mediated off-target binding of siRNA targeting human coagulation factor 7. RNA Biol 2012 9:87–97.
    doi: 10.4161/rna.9.1.18121pmc: PMC3342946pubmed: 22258146google scholar: lookup
  90. Brodersen P, Voinnet O. Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 2009 10:141–148.
    doi: 10.1038/nrm2619pubmed: 19145236google scholar: lookup
  91. Hwang I. Cell-cell communication via extracellular membrane vesicles and its role in the immune response. Mol Cells 2013 36:105–111.
    doi: 10.1007/s10059-013-0154-2pmc: PMC3887950pubmed: 23807045google scholar: lookup
  92. Raabe CA, Tang TH, Brosius J, Rozhdestvensky TS. Biases in small RNA deep sequencing data. Nucleic Acids Res 2014 42:1414–1426.
    doi: 10.1093/nar/gkt1021pmc: PMC3919602pubmed: 24198247google scholar: lookup
  93. National Research Council. Guide for the care and use of laboratory animals, 8th ed. 2011.
  94. Friedländer MR, Mackowiak SD, Li N, Chen W, Rajewsky N. miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res 2012 40:37–52.
    doi: 10.1093/nar/gkr688pmc: PMC3245920pubmed: 21911355google scholar: lookup
  95. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blocker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guerin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Roed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Broad Institute Genome Sequencing Platform, Broad Institute Whole Genome Assembly Team, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 2009 326:865–867.
    doi: 10.1126/science.1178158pmc: PMC3785132pubmed: 19892987google scholar: lookup
  96. Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 2011 39:D152–D157.
    doi: 10.1093/nar/gkq1027pmc: PMC3013655pubmed: 21037258google scholar: lookup
  97. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 2014 42:D68–D73.
    doi: 10.1093/nar/gkt1181pmc: PMC3965103pubmed: 24275495google scholar: lookup
  98. Chan PP, Lowe TM. GtRNAdb: a database of transfer RNA genes detected in genomic sequence. Nucleic Acids Res 2009 37:D93–D97.
    doi: 10.1093/nar/gkn787pmc: PMC2686519pubmed: 18984615google scholar: lookup
  99. Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 2015 43:D146–D152.
    doi: 10.1093/nar/gkᄄpmc: PMC4383922pubmed: 25378301google scholar: lookup
  100. Vlachos IS, Paraskevopoulou MD, Karagkouni D, Georgakilas G, Vergoulis T, Kanellos I, Anastasopoulos IL, Maniou S, Karathanou K, Kalfakakou D, Fevgas A, Dalamagas T, Hatzigeorgiou AG. DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions. Nucleic Acids Res 2015 43:D153–D159.
    doi: 10.1093/nar/gkሕpmc: PMC4383989pubmed: 25416803google scholar: lookup
  101. Chou CH, Chang NW, Shrestha S, Hsu SD, Lin YL, Lee WH, Yang CD, Hong HC, Wei TY, Tu SJ, Tsai TR, Ho SY, Jian TY, Wu HY, Chen PR, Lin NC, Huang HT, Yang TL, Pai CY, Tai CS, Chen WL, Huang CY, Liu CC, Weng SL, Liao KW, Hsu WL, Huang HD. miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res 2016 44:D239–D247.
    doi: 10.1093/nar/gkv1258pmc: PMC4702890pubmed: 26590260google scholar: lookup
  102. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. Elife 2015 4:e05005.
    doi: 10.7554/eLife.05005pmc: PMC4532895pubmed: 26267216google scholar: lookup
  103. Mann M, Wright PR, Backofen R. IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions. Nucleic Acids Res 2017 45:W435–W439.
    doi: 10.1093/nar/gkx279pmc: PMC5570192pubmed: 28472523google scholar: lookup
  104. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA 2004 10:1507–1517.
    doi: 10.1261/rna.5248604pmc: PMC1370637pubmed: 15383676google scholar: lookup
  105. Ghoshal A, Shankar R, Bagchi S, Grama A, Chaterji S. MicroRNA target prediction using thermodynamic and sequence curves. BMC Genomics 2015 16:999.
    doi: 10.1186/s12864-015-1933-2pmc: PMC4658802pubmed: 26608597google scholar: lookup
  106. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009 4:44–57.
    doi: 10.1038/nprot.2008.211pubmed: 19131956google scholar: lookup
  107. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009 37:1–13.
    doi: 10.1093/nar/gkn923pmc: PMC2615629pubmed: 19033363google scholar: lookup
  108. Mi H, Huang X, Muruganujan A, Tang H, Mills C, Kang D, Thomas PD. PANTHER version 11: expanded annotation data from gene ontology and reactome pathways, and data analysis tool enhancements. Nucleic Acids Res 2017 45:D183–D189.
    doi: 10.1093/nar/gkw1138pmc: PMC5210595pubmed: 27899595google scholar: lookup
  109. Busk PK. A tool for design of primers for microRNA-specific quantitative RT-qPCR. BMC Bioinformatics 2014 15:29.
    doi: 10.1186/1471-2105-15-29pmc: PMC3922658pubmed: 24472427google scholar: lookup
  110. Cirera S, Busk PK. Quantification of miRNAs by a simple and specific qPCR method. Methods Mol Biol 2014 1182:73–81.
    doi: 10.1007/978-1-4939-1062-5_7pubmed: 25055902google scholar: lookup
  111. Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, Moorman AF. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res 2009 37:e45.
    doi: 10.1093/nar/gkp045pmc: PMC2665230pubmed: 19237396google scholar: lookup
  112. Andersen CL, Jensen JL, Orntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 2004 64:5245–5250.
    doi: 10.1158/0008-5472.CAN-04-0496pubmed: 15289330google scholar: lookup
  113. Carossino M, Loynachan AT, James MacLachlan N, Drew C, Shuck KM, Timoney PJ, Del Piero F, Balasuriya UB. Detection of equine arteritis virus by two chromogenic RNA in situ hybridization assays (conventional and RNAscope(R)) and assessment of their performance in tissues from aborted equine fetuses. Arch Virol 2016 Aug 19.
    doi: 10.1007/s00705-016-3014-5pubmed: 27541817google scholar: lookup
  114. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008 3:1101–1108.
    doi: 10.1038/nprot.2008.73pubmed: 18546601google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.