FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Microbiol Spectr / Immune horses rapidly increase antileukoproteinase and lack ...
Microbiology spectrum2024; 12(10); e0109224; doi: 10.1128/spectrum.01092-24

Immune horses rapidly increase antileukoproteinase and lack type I interferon secretion during mucosal innate immune responses against equine herpesvirus type 1.

Abstract: Equine herpesvirus type 1 (EHV-1) is one of the most prevalent respiratory pathogens in horses with a high impact on animal health worldwide. Entry of the virus into epithelial cells of the upper respiratory tract and rapid local viral replication is followed by infection of local lymphoid tissues leading to cell-associated viremia and disease progression. Pre-existing mucosal immunity has previously been shown to reduce viral shedding and prevent viremia, consequently limiting severe disease manifestations. Here, nasopharyngeal transcriptomic profiling was used to identify differentially expressed genes following EHV-1 challenge in horses with different EHV-1 immune statuses. Immune horses (n = 4) did neither develop clinical disease nor viremia and did not shed virus after experimental infection, while non-immune horses (n = 4) did all the above. RNA sequencing was performed on nasopharyngeal samples pre- and 24 hours post-infection (24hpi). At 24hpi, 109 and 44 genes were upregulated in immune horses and non-immune horses, respectively, and three genes were explored in further detail. Antileukoproteinase (SLPI) gene expression increased 2.1-fold within 24 hours in immune horses in concert with protein secretion. Interferon (IFN)-induced proteins with tetratricopeptide repeats 2 (IFIT2) and 3 (IFIT3) were upregulated in non-immune horses, corresponding with nasal IFN-α secretion and viral replication. By contrast, neither IFIT expression nor IFN-α secretion was induced by EHV-1 infection of immune horses. Transcriptomic profiling offered a tool to identify, for the first time, the role of SLPI in innate immunity against EHV-1, and further emphasized the central role of the type I IFN response in the anti-viral defense of non-immune horses. Objective: Equine herpesvirus type 1 (EHV-1) remains a considerable concern in the equine industry, with yearly outbreaks resulting in morbidity, mortality, and economic losses. In addition to its importance in equine health, EHV-1 is a respiratory pathogen and an alphaherpesvirus, and it may serve as a model for other viruses with similar pathogenicity or phylogeny. Large animal models allow the collection of high-volume samples longitudinally, permitting in-depth investigation of immunological processes. This study was performed on bio-banked nasopharyngeal samples from an EHV-1 infection experiment, where clinical outcomes had previously been determined. Matched nucleic acid and protein samples throughout infection permitted longitudinal quantification of the protein or related proteins of selected differentially expressed genes detected during the transcriptomic screen. The results of this manuscript identified novel innate immune pathways of the upper respiratory tract during the first 24 hours of EHV-1 infection, offering a first look at the components of early mucosal immunity that are indicative of protection.
Get Full Text
Publication Date: 2024-08-20 PubMed ID: 39162558PubMed Central: PMC11448092DOI: 10.1128/spectrum.01092-24Google 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

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 research article investigates how a horse’s immune system responds to infection by equine herpesvirus type 1 (EHV-1), a common respiratory virus in horses. The study specifically focuses on differences in gene expression and immune response in horses with pre-existing immunity compared to those without.

Overview of Equine Herpesvirus type 1 (EHV-1)

  • This virus is a major respiratory pathogen in horses and has a significant impact on global horse health.
  • Early stages of the infection involve the virus entering epithelial cells of the upper respiratory tract, rapidly replicating and spreading to local lymphoid tissues, which leads to disease progression.
  • Previous studies have shown that horses with pre-existing mucosal immunity shed fewer viruses and are less likely to have viremia (viruses present in the blood), both of which contribute to less severe disease symptoms.

Objective and Methodology

  • The researchers sought to compare gene expression in immune and non-immune horses following exposure to EHV-1.
  • The immune horses in the study didn’t develop any disease symptoms, viremia, or shed the virus after being exposed to EHV-1. On the other hand, the non-immune horses react with typical disease symptoms.
  • The team performed RNA sequencing on nasopharyngeal samples from the horses both prior to and 24 hours after infection.

Key Findings

  • The researchers found that immune horses had an increased expression (2.1-fold) of the antileukoproteinase (SLPI) gene within 24 hours of infection. This was accompanied by protein secretion.
  • In non-immune horses, there was an increase in expression of Interferon (IFN)-induced proteins which was associated with nasal IFN-α secretion and viral replication.
  • One remarkable finding was that neither SLPI expression nor IFN-α secretion was observed in EHV-1 infection of immune horses, highlighting different immune response mechanisms in immune and non-immune horses.

Concluding Remarks and Future Implications

  • The study was able to pinpoint the role of SLPI in the innate immunity of horses against EHV-1 for the first time. It also reinforced the centrality of the type I IFN response in the anti-viral defence of non-immune horses.
  • The team suggest that the novel immune pathways they’ve highlighted could be key to understanding early mucosal immunity and designing better strategies for protection against EHV-1 infection.

Cite This Article

APA
Holmes CM, Babasyan S, Eady N, Schnabel CL, Wagner B. (2024). Immune horses rapidly increase antileukoproteinase and lack type I interferon secretion during mucosal innate immune responses against equine herpesvirus type 1. Microbiol Spectr, 12(10), e0109224. https://doi.org/10.1128/spectrum.01092-24

Publication

Microbiology spectrum
ISSN: 2165-0497
NlmUniqueID: 101634614
Country: United States
Language: English
Volume: 12
Issue: 10
Pages: e0109224

Researcher Affiliations

Holmes, Camille M
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Babasyan, Susanna
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Eady, Naya
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Schnabel, Christiane L
  • Biotechnological-Biomedical Center, Leipzig University, Leipzig, Germany.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Horses
  • Herpesvirus 1, Equid / immunology
  • Herpesvirus 1, Equid / genetics
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Immunity, Innate
  • Horse Diseases / virology
  • Horse Diseases / immunology
  • Interferon Type I / immunology
  • Interferon Type I / genetics
  • Interferon Type I / metabolism
  • Immunity, Mucosal
  • Gene Expression Profiling
  • Virus Shedding
  • Virus Replication
  • Viremia / immunology
  • Viremia / veterinary
  • Nasopharynx / virology
  • Nasopharynx / immunology

Grant Funding

  • Harry M. Zweig Memorial Fund for Equine Research
  • U.S. Department of Agriculture (USDA)
  • USDA | National Institute of Food and Agriculture (NIFA)

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 79 references
  1. García-Sastre A, Biron CA. Type 1 interferons and the virus-host relationship: a lesson in détente. Science 312:879–882.
    doi: 10.1126/science.1125676pubmed: 16690858google scholar: lookup
  2. Lehmann R, Müller MM, Klassert TE, Driesch D, Stock M, Heinrich A, Conrad T, Moore C, Schier UK, Guthke R, Slevogt H. Differential regulation of the transcriptomic and secretomic landscape of sensor and effector functions of human airway epithelial cells. Mucosal Immunol 11:627–642.
    doi: 10.1038/mi.2017.100pubmed: 29297499google scholar: lookup
  3. Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Sci Immunol 6:eabj5129.
    doi: 10.1126/sciimmunol.abj5129pmc: PMC8762609pubmed: 34890255google scholar: lookup
  4. Bagga B, Cehelsky JE, Vaishnaw A, Wilkinson T, Meyers R, Harrison LM, Roddam PL, Walsh EE, DeVincenzo JP. Effect of preexisting serum and mucosal antibody on experimental respiratory syncytial virus (RSV). J Infect Dis 212:1719–1725.
    doi: 10.1093/infdis/jiv281pubmed: 25977264google scholar: lookup
  5. Schmidt ME, Varga SM. The CD8 T cell response to respiratory virus infections. Front Immunol 9:678.
    doi: 10.3389/fimmu.2018.00678pmc: PMC5900024pubmed: 29686673google scholar: lookup
  6. Culley FJ. Natural killer cells in infection and inflammation of the lung. Immunology 128:151–163.
    doi: 10.1111/j.1365-2567.2009.03167.xpmc: PMC2767305pubmed: 19740372google scholar: lookup
  7. Westphalen K, Gusarova GA, Islam MN, Subramanian M, Cohen TS, Prince AS, Bhattacharya J. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Nature 506:503–506.
    doi: 10.1038/nature12902pmc: PMC4117212pubmed: 24463523google scholar: lookup
  8. Bourdonnay E, Zasłona Z, Penke LRK, Speth JM, Schneider DJ, Przybranowski S, Swanson JA, Mancuso P, Freeman CM, Curtis JL, Peters-Golden M. Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling. J Exp Med 212:729–742.
    doi: 10.1084/jem.20141675pmc: PMC4419346pubmed: 25847945google scholar: lookup
  9. Van de Walle GR, Jarosinski KW, Osterrieder N. Alphaherpesviruses and chemokines: pas de deux not yet brought to perfection. J Virol 82:6090–6097.
    doi: 10.1128/JVI.00098-08pmc: PMC2447056pubmed: 18385255google scholar: lookup
  10. Gilkerson JR, Whalley JM, Drummer HE, Studdert MJ, Love DN. Epidemiological studies of equine herpesvirus 1 (EHV-1) in Thoroughbred foals: a review of studies conducted in the Hunter Valley of New South Wales between 1995 and 1997. Vet Microbiol 68:15–25.
    doi: 10.1016/s0378-1135(99)00057-7pubmed: 10501158google scholar: lookup
  11. Edington N, Bridges CG, Huckle A. Experimental reactivation of equid herpesvirus 1 (EHV 1) following the administration of corticosteroids. Equine Vet J 17:369–372.
    doi: 10.1111/j.2042-3306.1985.tb02524.xpubmed: 2996879google scholar: lookup
  12. Burrows R, Goodridge D. Studies of persistent and latent equid herpesvirus 1 and herpesvirus 3 infections in the pirbright pony herd, p 307–319. .
  13. Lunn DP, Davis-Poynter N, Flaminio M, Horohov DW, Osterrieder K, Pusterla N, Townsend HGG. Equine herpesvirus-1 consensus statement. J Vet Intern Med 23:450–461.
    doi: 10.1111/j.1939-1676.2009.0304.xpubmed: 19645832google scholar: lookup
  14. Perkins GA, Goodman LB, Tsujimura K, Van de Walle GR, Kim SG, Dubovi EJ, Osterrieder N. Investigation of the prevalence of neurologic equine herpes virus type 1 (EHV-1) in a 23-year retrospective analysis (1984–2007). Vet Microbiol 139:375–378.
    doi: 10.1016/j.vetmic.2009.06.033pubmed: 19615831google scholar: lookup
  15. Perkins G, Babasyan S, Stout AE, Freer H, Rollins A, Wimer CL, Wagner B. Intranasal IgG4/7 antibody responses protect horses against equid herpesvirus-1 (EHV-1) infection including nasal virus shedding and cell-associated viremia. Virology 531:219–232.
    doi: 10.1016/j.virol.2019.03.014pubmed: 30928700google scholar: lookup
  16. Schnabel CL, Babasyan S, Rollins A, Freer H, Wimer CL, Perkins GA, Raza F, Osterrieder N, Wagner B. An equine herpesvirus type 1 (EHV-1) Ab4 open reading frame 2 deletion mutant provides immunity and protection from EHV-1 infection and disease. J Virol 93:e01011-19.
    doi: 10.1128/JVI.01011-19pmc: PMC6819910pubmed: 31462575google scholar: lookup
  17. Osterrieder N, Van de Walle GR. Pathogenic potential of equine alphaherpesviruses: the importance of the mononuclear cell compartment in disease outcome. Vet Microbiol 143:21–28.
    doi: 10.1016/j.vetmic.2010.02.010pubmed: 20202764google scholar: lookup
  18. Goehring LS, van Winden SC, van Maanen C, Sloet van Oldruitenborgh-Oosterbaan MM. Equine herpesvirus type 1-associated myeloencephalopathy in the Netherlands: a four-year retrospective study (1999-2003). J Vet Intern Med 20:601–607.
    doi: 10.1892/0891-6640(2006)20[601:ehtami]2.0.co;2pubmed: 16734096google scholar: lookup
  19. Kydd JH, Townsend HGG, Hannant D. The equine immune response to equine herpesvirus-1: the virus and its vaccines. Vet Immunol Immunopathol 111:15–30.
    doi: 10.1016/j.vetimm.2006.01.005pubmed: 16476492google scholar: lookup
  20. Pusterla N, David Wilson W, Madigan JE, Ferraro GL. Equine herpesvirus-1 myeloencephalopathy: a review of recent developments. Vet J 180:279–289.
    doi: 10.1016/j.tvjl.2008.08.004pubmed: 18805030google scholar: lookup
  21. Edington N, Smyth B, Griffiths L. The role of endothelial cell infection in the endometrium, placenta and foetus of equid herpesvirus 1 (EHV-1) abortions. J Comp Pathol 104:379–387.
    doi: 10.1016/s0021-9975(08)80148-xpubmed: 1651960google scholar: lookup
  22. Smith KC, Mumford JA, Lakhani K. A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus. J Comp Pathol 114:231–247.
    doi: 10.1016/s0021-9975(96)80045-4pubmed: 8762581google scholar: lookup
  23. Reed SM, Toribio RE. Equine herpesvirus 1 and 4. Vet Clin North Am Equine Pract 20:631–642.
    doi: 10.1016/j.cveq.2004.09.001pubmed: 15519823google scholar: lookup
  24. Kydd JH, Smith KC, Hannant D, Livesay GJ, Mumford JA. Distribution of equid herpesvirus-1 (EHV-1) in the respiratory tract of ponies: implications for vaccination strategies. Equine Vet J 26:466–469.
    doi: 10.1111/j.2042-3306.1994.tb04051.xpubmed: 7889920google scholar: lookup
  25. Kydd JH, Hannant D, Mumford JA. Residence and recruitment of leucocytes to the equine lung after EHV-1 infection. Vet Immunol Immunopathol 52:15–26.
    doi: 10.1016/0165-2427(95)05533-9pubmed: 8807773google scholar: lookup
  26. Breathnach CC, Soboll G, Suresh M, Lunn DP. Equine herpesvirus-1 infection induces IFN-γ production by equine T lymphocyte subsets. Vet Immunol Immunopathol 103:207–215.
    doi: 10.1016/j.vetimm.2004.09.024pubmed: 15621307google scholar: lookup
  27. Eady NA, Holmes C, Schnabel C, Babasyan S, Wagner B. Equine herpesvirus type 1 (EHV-1) replication at the upper respiratory entry site is inhibited by neutralizing EHV-1-specific IgG1 and IgG4/7 mucosal antibodies. J Virol 98:e0025024.
    doi: 10.1128/jvi.00250-24pmc: PMC11237562pubmed: 38742875google scholar: lookup
  28. Wimer CL, Schnabel CL, Perkins G, Babasyan S, Freer H, Stout AE, Rollins A, Osterrieder N, Goodman LB, Glaser A, Wagner B. The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses. PLoS ONE 13:e0206679.
    doi: 10.1371/journal.pone.0206679pmc: PMC6237298pubmed: 30440016google scholar: lookup
  29. Schnabel CL, Wimer CL, Perkins G, Babasyan S, Freer H, Watts C, Rollins A, Osterrieder N, Wagner B. Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity. BMC Vet Res 14:245.
    doi: 10.1186/s12917-018-1563-4pmc: PMC6106926pubmed: 30134896google scholar: lookup
  30. Gryspeerdt AC, Vandekerckhove AP, Baghi HB, Van de Walle GR, Nauwynck HJ. Expression of late viral proteins is restricted in nasal mucosal leucocytes but not in epithelial cells during early-stage equine herpes virus-1 infection. Vet J 193:576–578.
    doi: 10.1016/j.tvjl.2012.01.022pubmed: 22425309google scholar: lookup
  31. Vandekerckhove AP, Glorieux S, Gryspeerdt AC, Steukers L, Duchateau L, Osterrieder N, Van de Walle GR, Nauwynck HJ. Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants. J Gen Virol 91:2019–2028.
    doi: 10.1099/vir.0.019257-0pubmed: 20427565google scholar: lookup
  32. Bannazadeh Baghi H, Nauwynck HJ. Effect of equine herpesvirus type 1 (EHV-1) infection of nasal mucosa epithelial cells on integrin alpha 6 and on different components of the basement membrane. Arch Virol 161:103–110.
    doi: 10.1007/s00705-015-2643-4pubmed: 26497179google scholar: lookup
  33. Baghi HB, Nauwynck HJ. Impact of equine herpesvirus type 1 (EHV-1) infection on the migration of monocytic cells through equine nasal mucosa. Comp Immunol Microbiol Infect Dis 37:321–329.
    doi: 10.1016/j.cimid.2014.09.004pubmed: 25456193google scholar: lookup
  34. Zhao J, Poelaert KCK, Van Cleemput J, Nauwynck HJ. CCL2 and CCL5 driven attraction of CD172a+ monocytic cells during an equine herpesvirus type 1 (EHV-1) infection in equine nasal mucosa and the impact of two migration inhibitors, rosiglitazone (RSG) and quinacrine (QC). Vet Res 48:14.
    doi: 10.1186/s13567-017-0419-4pmc: PMC5327560pubmed: 28241864google scholar: lookup
  35. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 326:865–867.
    doi: 10.1126/science.1178158pmc: PMC3785132pubmed: 19892987google scholar: lookup
  36. Sajuthi SP, Everman JL, Jackson ND, Saef B, Rios CL, Moore CM, Mak ACY, Eng C, Fairbanks-Mahnke A, Salazar S. Nasal airway transcriptome-wide association study of asthma reveals genetically driven mucus pathobiology. Nat Commun 13:1632.
    doi: 10.1038/s41467-022-28973-7pmc: PMC8960819pubmed: 35347136google scholar: lookup
  37. Wesolowska-Andersen A, Everman JL, Davidson R, Rios C, Herrin R, Eng C, Janssen WJ, Liu AH, Oh SS, Kumar R, Fingerlin TE, Rodriguez-Santana J, Burchard EG, Seibold MA. Dual RNA-seq reveals viral infections in asthmatic children without respiratory illness which are associated with changes in the airway transcriptome. Genome Biol 18:12.
    doi: 10.1186/s13059-016-1140-8pmc: PMC5244706pubmed: 28103897google scholar: lookup
  38. Zarski LM, Weber PSD, Lee Y, Soboll Hussey G. Transcriptomic profiling of equine and viral genes in peripheral blood mononuclear cells in horses during equine herpesvirus 1 infection. Pathogens 10:43.
    doi: 10.3390/pathogens10010043pmc: PMC7825769pubmed: 33430330google scholar: lookup
  39. Lee CH, Igarashi Y, Hohman RJ, Kaulbach H, White MV, Kaliner MA. Distribution of secretory leukoprotease inhibitor in the human nasal airway. Am Rev Respir Dis 147:710–716.
    doi: 10.1164/ajrccm/147.3.710pubmed: 8095126google scholar: lookup
  40. Holmes CM, Babasyan S, Wagner B. Neonatal and maternal upregulation of antileukoproteinase in horses. Front Immunol 15:1395030.
    doi: 10.3389/fimmu.2024.1395030pmc: PMC11082313pubmed: 38736885google scholar: lookup
  41. Miller KW, Evans RJ, Eisenberg SP, Thompson RC. Secretory leukocyte protease inhibitor binding to mRNA and DNA as a possible cause of toxicity to Escherichia coli. J Bacteriol 171:2166–2172.
    doi: 10.1128/jb.171.4.2166-2172.1989pmc: PMC209873pubmed: 2467900google scholar: lookup
  42. Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH. Antibacterial activity of antileukoprotease. Infect Immun 64:4520–4524.
    doi: 10.1128/iai.64.11.4520-4524.1996pmc: PMC174407pubmed: 8890201google scholar: lookup
  43. Ding A, Thieblemont N, Zhu J, Jin F, Zhang J, Wright S. Secretory leukocyte protease inhibitor interferes with uptake of lipopolysaccharide by macrophages. Infect Immun 67:4485–4489.
    doi: 10.1128/IAI.67.9.4485-4489.1999pmc: PMC96768pubmed: 10456890google scholar: lookup
  44. Taggart CC, Greene CM, McElvaney NG, O’Neill S. Secretory leucoprotease inhibitor prevents lipopolysaccharide-induced IκBα degradation without affecting phosphorylation or ubiquitination. J Biol Chem 277:33648–33653.
    doi: 10.1074/jbc.M203710200pubmed: 12084717google scholar: lookup
  45. Taggart CC, Cryan S-A, Weldon S, Gibbons A, Greene CM, Kelly E, Low TB, O’neill SJ, McElvaney NG. Secretory leucoprotease inhibitor binds to NF-κB binding sites in monocytes and inhibits p65 binding. J Exp Med 202:1659–1668.
    doi: 10.1084/jem.20050768pmc: PMC2212970pubmed: 16352738google scholar: lookup
  46. Wright CD, Kennedy JA, Zitnik RJ, Kashem MA. Inhibition of murine neutrophil serine proteinases by human and murine secretory leukocyte protease inhibitor. Biochem Biophys Res Commun 254:614–617.
    doi: 10.1006/bbrc.1998.0108pubmed: 9920787google scholar: lookup
  47. McNeely TB, Dealy M, Dripps DJ, Orenstein JM, Eisenberg SP, Wahl SM. Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro. J Clin Invest 96:456–464.
    doi: 10.1172/JCI118056pmc: PMC185219pubmed: 7615818google scholar: lookup
  48. Skeate JG, Porras TB, Woodham AW, Jang JK, Taylor JR, Brand HE, Kelly TJ, Jung JU, Da Silva DM, Yuan W, Martin Kast W. Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection. J Gen Virol 97:422–434.
    doi: 10.1099/jgv.0.000341pmc: PMC4804641pubmed: 26555393google scholar: lookup
  49. Fakioglu E, Wilson SS, Mesquita PMM, Hazrati E, Cheshenko N, Blaho JA, Herold BC. Herpes simplex virus downregulates secretory leukocyte protease inhibitor: a novel immune evasion mechanism. J Virol 82:9337–9344.
    doi: 10.1128/JVI.00603-08pmc: PMC2546954pubmed: 18667508google scholar: lookup
  50. Keller MJ, Huber A, Espinoza L, Serrano MG, Parikh HI, Buck GA, Gold JA, Wu Y, Wang T, Herold BC. Impact of herpes simplex virus type 2 and human immunodeficiency virus dual infection on female genital tract mucosal immunity and the vaginal microbiome. J Infect Dis 220:852–861.
    doi: 10.1093/infdis/jiz203pmc: PMC6667798pubmed: 31111902google scholar: lookup
  51. Woodham AW, Da Silva DM, Skeate JG, Raff AB, Ambroso MR, Brand HE, Isas JM, Langen R, Kast WM. The S100A10 subunit of the annexin A2 heterotetramer facilitates L2-mediated human papillomavirus infection. PLoS One 7:e43519.
    doi: 10.1371/journal.pone.0043519pmc: PMC3425544pubmed: 22927980google scholar: lookup
  52. Telford EAR, Watson MS, McBride K, Davison AJ. The DNA sequence of equine herpesvirus-1. Virology 189:304–316.
    doi: 10.1016/0042-6822(92)90706-Upubmed: 1318606google scholar: lookup
  53. Liu Y, Beyer A, Aebersold R. On the dependency of cellular protein levels on mRNA abundance. Cell 165:535–550.
    doi: 10.1016/j.cell.2016.03.014pubmed: 27104977google scholar: lookup
  54. Yang Z, Liang H, Zhou Q, Li Y, Chen H, Ye W, Chen D, Fleming J, Shu H, Liu Y. Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms. Cell Res 22:1328–1338.
    doi: 10.1038/cr.2012.111pmc: PMC3434343pubmed: 22825553google scholar: lookup
  55. Stawowczyk M, Van Scoy S, Kumar KP, Reich NC. The interferon stimulated gene 54 promotes apoptosis. J Biol Chem 286:7257–7266.
    doi: 10.1074/jbc.M110.207068pmc: PMC3044982pubmed: 21190939google scholar: lookup
  56. Liu Y, Zhang Y-B, Liu T-K, Gui J-F. Lineage-specific expansion of IFIT gene family: an insight into coevolution with IFN gene family. PLoS One 8:e66859.
    doi: 10.1371/journal.pone.0066859pmc: PMC3688568pubmed: 23818968google scholar: lookup
  57. Chen L, Liu S, Xu F, Kong Y, Wan L, zhang Y, Zhang Z. Inhibition of proteasome activity induces aggregation of IFIT2 in the centrosome and enhances IFIT2-induced cell apoptosis. Int J Biol Sci 13:383–390.
    doi: 10.7150/ijbs.17236pmc: PMC5370445pubmed: 28367102google scholar: lookup
  58. Berchtold S, Manncke B, Klenk J, Geisel J, Autenrieth IB, Bohn E. Forced IFIT-2 expression represses LPS induced TNF-alpha expression at posttranscriptional levels. BMC Immunol 9:75.
    doi: 10.1186/1471-2172-9-75pmc: PMC2632614pubmed: 19108715google scholar: lookup
  59. Stawowczyk M, Naseem S, Montoya V, Baker DP, Konopka J, Reich NC. Pathogenic effects of IFIT2 and interferon-β during fatal systemic Candida albicans infection. mBio 9:e00365-18.
    doi: 10.1128/mBio.00365-18pmc: PMC5904408pubmed: 29666281google scholar: lookup
  60. Cho H, Shrestha B, Sen GC, Diamond MS. A role for IFIT2 in restricting West Nile virus infection in the brain. J Virol 87:8363–8371.
    doi: 10.1128/JVI.01097-13pmc: PMC3719802pubmed: 23740986google scholar: lookup
  61. Davis BM, Fensterl V, Lawrence TM, Hí«Žk AW, Sen GC, Schnell MJ. IFIT2 is a restriction factor in Rabies virus pathogenicity. J Virol 91:e00889-17.
    doi: 10.1128/JVI.00889-17pmc: PMC5553164pubmed: 28637751google scholar: lookup
  62. Fensterl V, Wetzel JL, Ramachandran S, Ogino T, Stohlman SA, Bergmann CC, Diamond MS, Virgin HW, Sen GC. Interferon-induced IFIT2/ISG54 protects mice from lethal VSV neuropathogenesis. PLoS Pathog 8:e1002712.
    doi: 10.1371/journal.ppat.1002712pmc: PMC3355090pubmed: 22615570google scholar: lookup
  63. Fensterl V, Wetzel JL, Sen GC. Interferon-induced protein IFIT2 protects mice from infection of the peripheral nervous system by vesicular Stomatitis virus. J Virol 88:10303–10311.
    doi: 10.1128/JVI.01341-14pmc: PMC4178895pubmed: 24991014google scholar: lookup
  64. Butchi NB, Hinton DR, Stohlman SA, Kapil P, Fensterl V, Sen GC, Bergmann CC. IFIT2 deficiency results in uncontrolled neurotropic coronavirus replication and enhanced encephalitis via impaired alpha/beta interferon induction in macrophages. J Virol 88:1051–1064.
    doi: 10.1128/JVI.02272-13pmc: PMC3911674pubmed: 24198415google scholar: lookup
  65. Baxi MK, Efstathiou S, Lawrence G, Whalley JM, Slater JD, Field HJ. The detection of latency-associated transcripts of equine herpesvirus 1 in ganglionic neurons. J Gen Virol 76:3113–3118.
    doi: 10.1099/0022-1317-76-12-3113pubmed: 8847517google scholar: lookup
  66. Jiang Z, Su C, Zheng C. Herpes simplex virus 1 tegument protein Ul41 counteracts IFIT2 antiviral innate immunity. J Virol 90:11056–11061.
    doi: 10.1128/JVI.01672-16pmc: PMC5126364pubmed: 27681138google scholar: lookup
  67. Xiao S, Li D, Zhu H-Q, Song M-G, Pan X-R, Jia P-M, Peng L-L, Dou A-X, Chen G-Q, Chen S-J, Chen Z, Tong J-H. RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins. Proc Natl Acad Sci U S A 103:16448–16453.
    doi: 10.1073/pnas.0607830103pmc: PMC1637602pubmed: 17050680google scholar: lookup
  68. Wang J, Dai M, Cui Y, Hou G, Deng J, Gao X, Liao Z, Liu Y, Meng Y, Wu L, Yao C, Wang Y, Qian J, Guo Q, Ding H, Qu B, Shen N. Association of abnormal elevations in IFIT 3 with overactive cyclicgmp–ampsynthase/stimulator of interferon genes signaling in human systemic lupus erythematosus monocytes. Arthritis Rheumatol 70:2036–2045.
    doi: 10.1002/art.40576pubmed: 29806091google scholar: lookup
  69. Liu X-Y, Chen W, Wei B, Shan Y-F, Wang C. IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. J Immunol 187:2559–2568.
    doi: 10.4049/jimmunol.1100963pubmed: 21813773google scholar: lookup
  70. Edington N, Bridges CG, Griffiths L. Equine interferons following exposure to equid herpesvirus-1 or -4. J Interferon Res 9:389–392.
    doi: 10.1089/jir.1989.9.389pubmed: 2474039google scholar: lookup
  71. Chong YC, Duffus WPH. Immune responses of specific pathogen free foals to EHV-1 infection. Vet Microbiol 32:215–228.
    doi: 10.1016/0378-1135(92)90146-kpubmed: 1280876google scholar: lookup
  72. Ge SX, Son EW, Yao R. iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinformatics 19:534.
    doi: 10.1186/s12859-018-2486-6pmc: PMC6299935pubmed: 30567491google scholar: lookup
  73. Hotelling H. Analysis of a complex of statistical variables into principal components. J Educ Psychol 24:417–441.
    doi: 10.1037/h0071325google scholar: lookup
  74. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550.
    doi: 10.1186/s13059-014-0550-8pmc: PMC4302049pubmed: 25516281google scholar: lookup
  75. Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H, Vilo J. g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res 47:W191–W198.
    doi: 10.1093/nar/gkz369pmc: PMC6602461pubmed: 31066453google scholar: lookup
  76. Szklarczyk D, Gable AL, Nastou KC, Lyon D, Kirsch R, Pyysalo S, Doncheva NT, Legeay M, Fang T, Bork P, Jensen LJ, von Mering C. The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res 49:D605–D612.
    doi: 10.1093/nar/gkaa1074pmc: PMC7779004pubmed: 33237311google scholar: lookup
  77. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504.
    doi: 10.1101/gr.1239303pmc: PMC403769pubmed: 14597658google scholar: lookup
  78. Wagner B, Freer H. Development of a bead-based multiplex assay for simultaneous quantification of cytokines in horses. Vet Immunol Immunopathol 127:242–248.
    doi: 10.1016/j.vetimm.2008.10.313pubmed: 19027964google scholar: lookup
  79. Ma G, Feineis S, Osterrieder N, Van de Walle GR. Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I. J Virol 86:3554–3563.
    doi: 10.1128/JVI.06994-11pmc: PMC3302497pubmed: 22278226google scholar: lookup
Subscribe to our newsletter
Join 99,357 horse owners like you who receive our email updates on horse health and nutrition.