FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Journal of virology2024; 98(6); e0025024; doi: 10.1128/jvi.00250-24

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.

Abstract: Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT provide the first line of defense against EHV-1 and are crucial for orchestrating immunity. To define host-pathogen interactions, we characterized B-cell responses, antibody isotype functions, and EHV-1 replication of susceptible (non-immune) and clinically protected (immune) horses after experimental EHV-1 infection. Nasal secretion and nasal wash samples were collected and used for the isolation of DNA, RNA, and mucosal antibodies. Shedding of infectious virus, EHV-1 copy numbers, viral RNA expression, and host B-cell activation in the URT were compared based on host immune status. Mucosal EHV-1-specific antibody responses were associated with EHV-1 shedding and viral RNA transcription. Finally, mucosal immunoglobulin G (IgG) and IgA isotypes were purified and tested for neutralizing capabilities. IgG1 and IgG4/7 neutralized EHV-1, while IgG3/5, IgG6, and IgA did not. Immune horses secreted high amounts of mucosal EHV-1-specific IgG4/7 antibodies and quickly upregulated B-cell pathway genes, while EHV-1 was undetected by virus isolation and PCR. RNA transcription analysis reinforced incomplete viral replication in immune horses. In contrast, complete viral replication with high viral copy numbers and shedding of infectious viruses was characteristic for non-immune horses, together with low or absent EHV-1-specific neutralizing antibodies during viral replication. These data confirm that pre-existing mucosal IgG1 and IgG4/7 and rapid B-cell activation upon EHV-1 infection are essential for virus neutralization, regulation of viral replication, and mucosal immunity against EHV-1.IMPORTANCEEquine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion storms, and neurologic outbreaks known as equine herpes myeloencephalopathy (EHM). EHV-1 is transmitted with respiratory secretions by nose-to-nose contact or via fomites. The virus initially infects the epithelium of the upper respiratory tract (URT). Host-pathogen interactions and mucosal immunity at the viral entry site provide the first line of defense against the EHV-1. Robust mucosal immunity can be essential in protecting against EHV-1 and to reduce EHM outbreaks. It has previously been shown that immune horses do not establish cell-associated viremia, the prerequisite for EHM. Here, we demonstrate how mucosal antibodies can prevent the replication of EHV-1 at the epithelium of the URT and, thereby, the progression of the virus to the peripheral blood. The findings improve the mechanistic understanding of mucosal immunity against EHV-1 and can support the development of enhanced diagnostic tools, vaccines against EHM, and the management of EHV-1 outbreaks.
Get Full Text
Publication Date: 2024-05-14 PubMed ID: 38742875PubMed Central: PMC11237562DOI: 10.1128/jvi.00250-24Google 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.

Equine herpesvirus type 1 (EHV-1) replication in the upper respiratory tract is inhibited by specific mucosal antibodies, particularly IgG1 and IgG4/7. Immune horses exhibit rapid B-cell responses and produce these neutralizing antibodies, preventing viral replication and shedding, whereas non-immune horses show extensive viral replication and low antibody response.

Background and Importance

  • EHV-1 is a contagious virus causing respiratory illness, abortion, and neurological disease (equine herpes myeloencephalopathy) in horses.
  • The virus spreads through respiratory secretions and initially infects the epithelial cells of the upper respiratory tract (URT).
  • Mucosal immunity at the URT entry site serves as the first line of defense by controlling viral replication and spread.
  • Understanding mucosal immune responses against EHV-1 is crucial for preventing disease progression and outbreaks.
  • Current research aims to identify which antibody types and immune mechanisms effectively neutralize the virus at this site.

Research Objective

  • To characterize B-cell mediated immune responses and antibody isotypes in the URT of susceptible (non-immune) and immune horses following experimental EHV-1 infection.
  • To determine the relationship between mucosal antibody types and the inhibition of EHV-1 replication and viral shedding.
  • To compare viral replication dynamics, host immune activation, and antibody neutralizing capabilities between immune and non-immune horses.

Methods

  • Experimental infection of both immune (previously exposed) and non-immune horses with EHV-1.
  • Collection of nasal secretions and nasal wash samples from the horses’ upper respiratory tract.
  • Isolation of DNA, RNA, and mucosal antibodies from these samples to assess:
    • Viral shedding (infectious virus presence)
    • Viral DNA copy numbers via PCR
    • Viral RNA expression (transcription)
    • Host B-cell activation markers
  • Purification of mucosal immunoglobulin isotypes (IgG1, IgG3/5, IgG4/7, IgG6, and IgA) for neutralization assays against EHV-1.

Key Findings

  • Immune horses had undetectable or very low levels of viral replication and shedding, confirmed by negative virus isolation and PCR results.
  • Non-immune horses exhibited high viral DNA copy numbers, active viral RNA transcription, and significant shedding of infectious virus.
  • Mucosal antibodies IgG1 and IgG4/7 were found to effectively neutralize EHV-1, while other isotypes (IgG3/5, IgG6, IgA) did not show such neutralization capabilities.
  • Immune horses secreted high levels of EHV-1-specific IgG4/7 antibodies in the nasal mucosa and rapidly upregulated genes involved in B-cell activation pathways.
  • Non-immune horses lacked sufficient mucosal neutralizing antibodies during the peak of viral replication, highlighting vulnerability to virus spread.
  • RNA transcription analyses indicated incomplete viral replication in immune horses, supporting the protective role of mucosal immunity.

Implications

  • Pre-existing mucosal IgG1 and IgG4/7 antibodies are critical for early neutralization of EHV-1 at the virus entry site in the URT.
  • Rapid activation of mucosal B-cells upon infection enhances protective immunity, preventing both viral replication locally and systemic dissemination.
  • This study reinforces the importance of mucosal immunity in controlling EHV-1 infections, potentially blocking progression to viremia and neurological disease.
  • Findings could direct the development of improved vaccines targeting mucosal immune responses, aiming to reduce the incidence of EHM outbreaks.
  • The results also offer insights for enhanced diagnostic tools to monitor mucosal antibody responses and infection status in horses.

Conclusion

  • The study demonstrates that specific mucosal IgG1 and IgG4/7 antibodies effectively neutralize EHV-1 replication in the upper respiratory tract.
  • Immune horses control viral infection by rapid activation of B-cells and producing neutralizing antibodies, whereas non-immune horses show uncontrolled viral replication.
  • Understanding these host-pathogen interactions at the mucosal level facilitates better management of EHV-1 infection and informs vaccine strategies to prevent severe disease outcomes.

Cite This Article

APA
Eady NA, Holmes C, Schnabel C, Babasyan S, Wagner B. (2024). 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(6), e0025024. https://doi.org/10.1128/jvi.00250-24

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 98
Issue: 6
Pages: e0025024
PII: e00250-24

Researcher Affiliations

Eady, Naya A
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Holmes, Camille
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Schnabel, Christiane
  • 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.
Wagner, Bettina
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Herpesvirus 1, Equid / immunology
  • Horses
  • Virus Replication
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / veterinary
  • Herpesviridae Infections / virology
  • Antibodies, Viral / immunology
  • Antibodies, Neutralizing / immunology
  • Horse Diseases / virology
  • Horse Diseases / immunology
  • Immunoglobulin G / immunology
  • Immunity, Mucosal
  • Virus Shedding / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • Host-Pathogen Interactions / immunology

Grant Funding

  • Harry M. Zweig Memorial Fund for Equine Research
  • 2015-67015-23091 / USDA | National Institute of Food and Agriculture (NIFA)

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 63 references
  1. Lunn DP, Davis‐Poynter N, Flaminio MJBF, 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
  2. 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
  3. Csellner H, Walker C, Wellington JE, McLure LE, Love DN, Whalley JM. EHV-1 glycoprotein D (EHV-1 gD) is required for virus entry and cell-cell fusion, and an EHV-1 gD deletion mutant induces a protective immune response in mice.. Arch Virol 145:2371–2385.
    doi: 10.1007/s007050070027pubmed: 11205124google scholar: lookup
  4. Frampton AR, Goins WF, Cohen JB, von Einem J, Osterrieder N, O’Callaghan DJ, Glorioso JC. Equine herpesvirus 1 utilizes a novel herpesvirus entry receptor.. J Virol 79:3169–3173.
    doi: 10.1128/JVI.79.5.3169-3173.2005pmc: PMC548480pubmed: 15709036google scholar: lookup
  5. Frampton AR, Uchida H, von Einem J, Goins WF, Grandi P, Cohen JB, Osterrieder N, Glorioso JC. Equine herpesvirus type 1 (EHV-1) utilizes microtubules, dynein, and ROCK1 to productively infect cells.. Vet Microbiol 141:12–21.
    doi: 10.1016/j.vetmic.2009.07.035pmc: PMC2819619pubmed: 19713056google scholar: lookup
  6. Azab W, Osterrieder N. Glycoproteins D of equine herpesvirus type 1 (EHV-1) and EHV-4 determine cellular tropism independently of integrins.. J Virol 86:2031–2044.
    doi: 10.1128/JVI.06555-11pmc: PMC3302398pubmed: 22171258google scholar: lookup
  7. Van de Walle GR, Peters ST, VanderVen BC, O’Callaghan DJ, Osterrieder N. Equine herpesvirus 1 entry via endocytosis is facilitated by αV integrins and an RSD motif in glycoprotein D.. J Virol 82:11859–11868.
    doi: 10.1128/JVI.00868-08pmc: PMC2583640pubmed: 18815313google scholar: lookup
  8. Kurtz BM, Singletary LB, Kelly SD, Frampton AR. Equus caballus major histocompatibility complex class I is an entry receptor for equine herpesvirus type 1.. J Virol 84:9027–9034.
    doi: 10.1128/JVI.00287-10pmc: PMC2937649pubmed: 20610718google scholar: lookup
  9. Sasaki M, Hasebe R, Makino Y, Suzuki T, Fukushi H, Okamoto M, Matsuda K, Taniyama H, Sawa H, Kimura T. Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D.. Genes Cells 16:343–357.
    doi: 10.1111/j.1365-2443.2011.01491.xpmc: PMC3118799pubmed: 21306483google scholar: lookup
  10. Sasaki M, Kim E, Igarashi M, Ito K, Hasebe R, Fukushi H, Sawa H, Kimura T. Single amino acid residue in the A2 domain of major histocompatibility complex class I is involved in the efficiency of equine herpesvirus-1 entry.. J Biol Chem 286:39370–39378.
    doi: 10.1074/jbc.M111.251751pmc: PMC3234761pubmed: 21949188google scholar: lookup
  11. Kremling V, Loll B, Pach S, Dahmani I, Weise C, Wolber G, Chiantia S, Wahl MC, Osterrieder N, Azab W. Crystal structures of glycoprotein D of equine alphaherpesviruses reveal potential binding sites to the entry receptor MHC-I.. Front Microbiol 14:1197120.
    doi: 10.3389/fmicb.2023.1197120pmc: PMC10213783pubmed: 37250020google scholar: lookup
  12. Gray WL, Baumann RP, Robertson AT, O’Callaghan DJ, Staczek J. Characterization and mapping of equine herpesvirus type 1 immediate early, early, and late transcripts.. Virus Res 8:233–244.
    doi: 10.1016/0168-1702(87)90018-9pubmed: 2825444google scholar: lookup
  13. Caughman GB, Staczek J, O’Callaghan DJ. Equine herpesvirus type 1 infected cell polypeptides: evidence for immediate early/early/late regulation of viral gene expression.. Virology 145:49–61.
    doi: 10.1016/0042-6822(85)90200-4pubmed: 2990102google scholar: lookup
  14. 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
  15. Smith RH, Zhao Y, O’Callaghan DJ. The equine herpesvirus 1 (EHV-1) UL3 gene, an ICP27 homolog, is necessary for full activation of gene expression directed by an EHV-1 late promoter.. J Virol 67:1105–1109.
    doi: 10.1128/JVI.67.2.1105-1109.1993pmc: PMC237469pubmed: 8380457google scholar: lookup
  16. Breathnach CC, Yeargan MR, Sheoran AS, Allen GP. The mucosal humoral immune response of the horse to infective challenge and vaccination with equine herpesvirus-1 antigens.. Equine Vet J 33:651–657.
    doi: 10.2746/042516401776249318pubmed: 11770985google scholar: lookup
  17. 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
  18. 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
  19. Wagner B, Perkins G, Babasyan S, Freer H, Keggan A, Goodman LB, Glaser A, Torsteinsdóttir S, Svansson V, Björnsdóttir S. Neonatal immunization with a single IL-4/antigen dose induces increased antibody responses after challenge infection with equine herpesvirus type 1 (EHV-1) at weanling age.. PLoS ONE 12:e0169072.
    doi: 10.1371/journal.pone.0169072pmc: PMC5207648pubmed: 28045974google scholar: lookup
  20. 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
  21. 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
  22. Perkins GA, Goodman LB, Dubovi EJ, Kim SG, Osterrieder N. Detection of equine herpesvirus‐1 in nasal swabs of horses by quantitative real‐time PCR.. J Vet Int Med 22:1234–1238.
    doi: 10.1111/j.1939-1676.2008.0172.xpubmed: 18691363google scholar: lookup
  23. Goodman LB, Wagner B, Flaminio MJBF, Sussman KH, Metzger SM, Holland R, Osterrieder N. Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type.. Vaccine 24:3636–3645.
    doi: 10.1016/j.vaccine.2006.01.062pubmed: 16513225google scholar: lookup
  24. Hussey GS, Hussey SB, Wagner B, Horohov DW, Van de Walle GR, Osterrieder N, Goehring LS, Rao S, Lunn DP. Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant.. Vet Res 42:23.
    doi: 10.1186/1297-9716-42-23pmc: PMC3045331pubmed: 21314906google scholar: lookup
  25. Larson EM, Wagner B. Viral infection and allergy – what equine immune responses can tell us about disease severity and protection.. Mol Immunol 135:329–341.
    doi: 10.1016/j.molimm.2021.04.013pubmed: 33975251google scholar: lookup
  26. Murphy KM, Weaver C. Janeway’s immunobiology.. 9th ed. GS, Garland Science, Taylor & Francis Group, New York, London..
  27. Lu LL, Suscovich TJ, Fortune SM, Alter G. Beyond binding: antibody effector functions in infectious diseases.. Nat Rev Immunol 18:46–61.
    doi: 10.1038/nri.2017.106pmc: PMC6369690pubmed: 29063907google scholar: lookup
  28. Varghese R, Mikyas Y, Stewart PL, Ralston R. Postentry neutralization of adenovirus type 5 by an antihexon antibody.. J Virol 78:12320–12332.
    doi: 10.1128/JVI.78.22.12320-12332.2004pmc: PMC525062pubmed: 15507619google scholar: lookup
  29. Ishii Y, Tanaka K, Kondo K, Takeuchi T, Mori S, Kanda T. Inhibition of nuclear entry of HPV16 pseudovirus-packaged DNA by an anti-HPV16 L2 neutralizing antibody.. Virology 406:181–188.
    doi: 10.1016/j.virol.2010.07.019pubmed: 20684966google scholar: lookup
  30. Aiyegbo MS, Sapparapu G, Spiller BW, Eli IM, Williams DR, Kim R, Lee DE, Liu T, Li S, Woods VL, Nannemann DP, Meiler J, Stewart PL, Crowe JE. Human rotavirus VP6-specific antibodies mediate intracellular neutralization by binding to a quaternary structure in the transcriptional pore.. PLoS One 8:e61101.
    doi: 10.1371/journal.pone.0061101pmc: PMC3650007pubmed: 23671563google scholar: lookup
  31. Zhou D, Zhang Y, Li Q, Chen Y, He B, Yang J, Tu H, Lei L, Yan H. Matrix protein-specific IgA antibody inhibits measles virus replication by intracellular neutralization.. J Virol 85:11090–11097.
    doi: 10.1128/JVI.00768-11pmc: PMC3194966pubmed: 21865386google scholar: lookup
  32. Wagner B, Miller DC, Lear TL, Antczak DF. The complete map of the Ig heavy chain constant gene region reveals evidence for seven IgG isotypes and for IgD in the horse.. J Immunol 173:3230–3242.
    doi: 10.4049/jimmunol.173.5.3230pubmed: 15322185google scholar: lookup
  33. Wagner B. Immunoglobulins and immunoglobulin genes of the horse.. Dev Comp Immunol 30:155–164.
    doi: 10.1016/j.dci.2005.06.008pubmed: 16046236google scholar: lookup
  34. Lewis MJ, Wagner B, Woof JM. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.. Mol Immunol 45:818–827.
    doi: 10.1016/j.molimm.2007.06.158pmc: PMC2075531pubmed: 17669496google scholar: lookup
  35. Keggan A, Freer H, Rollins A, Wagner B. Production of seven monoclonal equine immunoglobulins isotyped by multiplex analysis.. Vet Immunol Immunopathol 153:187–193.
    doi: 10.1016/j.vetimm.2013.02.010pmc: PMC10958203pubmed: 23541920google scholar: lookup
  36. Renegar KB, Small PA. Immunoglobulin A mediation of murine nasal anti-influenza virus immunity.. J Virol 65:2146–2148.
    doi: 10.1128/JVI.65.4.2146-2148.1991pmc: PMC240095pubmed: 2002558google scholar: lookup
  37. Lamm ME. Interaction of antigens and antibodies at mucosal surfaces.. Annu Rev Microbiol 51:311–340.
    doi: 10.1146/annurev.micro.51.1.311pubmed: 9343353google scholar: lookup
  38. van Erp EA, Luytjes W, Ferwerda G, van Kasteren PB. Fc-mediated antibody effector functions during respiratory syncytial virus infection and disease.. Front Immunol 10:548.
    doi: 10.3389/fimmu.2019.00548pmc: PMC6438959pubmed: 30967872google scholar: lookup
  39. Newcomb WW, Brown JC, Booy FP, Steven AC. Nucleocapsid mass and capsomer protein stoichiometry in equine herpesvirus 1: scanning transmission electron microscopic study.. J Virol 63:3777–3783.
    doi: 10.1128/JVI.63.9.3777-3783.1989pmc: PMC250970pubmed: 2760983google scholar: lookup
  40. Newcomb WW, Trus BL, Booy FP, Steven AC, Wall JS, Brown JC. Structure of the herpes simplex virus capsid molecular composition of the pentons and the triplexes.. J Mol Biol 232:499–511.
    doi: 10.1006/jmbi.1993.1406pubmed: 8393939google scholar: lookup
  41. Nicholson P, Addison C, Cross AM, Kennard J, Preston VG, Rixon FJ. Localization of the herpes simplex virus type 1 major capsid protein VP5 to the cell nucleus requires the abundant scaffolding protein VP22a.. J Gen Virol 75 (Pt 5):1091–1099.
    doi: 10.1099/0022-1317-75-5-1091pubmed: 8176370google scholar: lookup
  42. Rixon FJ, Addison C, McGregor A, Macnab SJ, Nicholson P, Preston VG, Tatman JD. Multiple interactions control the intracellular localization of the herpes simplex virus type 1 capsid proteins.. J Gen Virol 77 (Pt 9):2251–2260.
    doi: 10.1099/0022-1317-77-9-2251pubmed: 8811025google scholar: lookup
  43. Ebner PD, O’Callaghan DJ. Genetic complexity of EHV-1 defective interfering particles and identification of novel IR4/UL5 hybrid proteins produced during persistent infection.. Virus Genes 32:313–320.
    doi: 10.1007/s11262-005-6916-ypubmed: 16732484google scholar: lookup
  44. Kasem S, Yu MHH, Yamada S, Kodaira A, Matsumura T, Tsujimura K, Madbouly H, Yamaguchi T, Ohya K, Fukushi H. The ORF37 (UL24) is a neuropathogenicity determinant of equine herpesvirus 1 (EHV-1) in the mouse encephalitis model.. Virology 400:259–270.
    doi: 10.1016/j.virol.2010.02.012pubmed: 20199788google scholar: lookup
  45. 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
  46. Heming JD, Conway JF, Homa FL. Herpesvirus capsid assembly and DNA packaging, p 119–142.. In Osterrieder K (ed), Cell biology of herpes viruses. Springer International Publishing, Cham, Switzerland..
    pmc: PMC5548147pubmed: 28528442
  47. Koslowski KM, Shaver PR, Casey JT, Wilson T, Yamanaka G, Sheaffer AK, Tenney DJ, Pederson NE. Physical and functional interactions between the herpes simplex virus UL15 and UL28 DNA cleavage and packaging proteins.. J Virol 73:1704–1707.
    doi: 10.1128/JVI.73.2.1704-1707.1999pmc: PMC104003pubmed: 9882384google scholar: lookup
  48. Abbotts AP, Preston VG, Hughes M, Patel AH, Stow ND. Interaction of the herpes simplex virus type 1 packaging protein UL15 with full-length and deleted forms of the UL28 protein.. J Gen Virol 81:2999–3009.
    doi: 10.1099/0022-1317-81-12-2999pubmed: 11086131google scholar: lookup
  49. Beard PM, Taus NS, Baines JD. DNA cleavage and packaging proteins encoded by genes U28, U15, and U33 of herpes simplex virus type 1 form a complex in infected cells.. J Virol 76:4785–4791.
    doi: 10.1128/jvi.76.10.4785-4791.2002pmc: PMC136146pubmed: 11967295google scholar: lookup
  50. White CA, Stow ND, Patel AH, Hughes M, Preston VG. Herpes simplex virus type 1 portal protein UL6 interacts with the putative terminase subunits UL15 and UL28.. J Virol 77:6351–6358.
    doi: 10.1128/jvi.77.11.6351-6358.2003pmc: PMC154995pubmed: 12743292google scholar: lookup
  51. Beard PM, Baines JD. The DNA cleavage and packaging protein encoded by the UL33 gene of herpes simplex virus 1 associates with capsids.. Virology 324:475–482.
    doi: 10.1016/j.virol.2004.03.044pubmed: 15207632google scholar: lookup
  52. Jacobson JG, Yang K, Baines JD, Homa FL. Linker insertion mutations in the herpes simplex virus type 1 UL28 gene: effects on UL28 interaction with UL15 and UL33 and identification of a second-site mutation in the UL15 gene that suppresses a lethal UL28 mutation.. J Virol 80:12312–12323.
    doi: 10.1128/JVI.01766-06pmc: PMC1676265pubmed: 17035316google scholar: lookup
  53. Albright BS, Kosinski A, Szczepaniak R, Cook EA, Stow ND, Conway JF, Weller SK. The putative herpes simplex virus 1 chaperone protein UL32 modulates disulfide bond formation during infection.. J Virol 89:443–453.
    doi: 10.1128/JVI.01913-14pmc: PMC4301124pubmed: 25320327google scholar: lookup
  54. Anders S, Pyl PT, Huber W. HTSeq—a python framework to work with high-throughput sequencing data.. Bioinformatics 31:166–169.
    doi: 10.1093/bioinformatics/btu638pmc: PMC4287950pubmed: 25260700google scholar: lookup
  55. Li B, Dewey CN. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome.. BMC Bioinformatics 12:323.
    doi: 10.1186/1471-2105-12-323pmc: PMC3163565pubmed: 21816040google scholar: lookup
  56. 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
  57. 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.. Nucleic Acids Res 47:W191–W198.
    doi: 10.1093/nar/gkz369pmc: PMC6602461pubmed: 31066453google scholar: lookup
  58. Lunn DP, Holmes MA, Antczak DF, Agerwal N, Baker J, Bendali-Ahcene S, Blanchard-Channell M, Byrne KM, Cannizzo K, Davis W, Hamilton MJ, Hannant D, Kondo T, Kydd JH, Monier MC, Moore PF, O’Neil T, Schram BR, Sheoran A, Stott JL, Sugiura T, Vagnoni KE. Report of the second equine leucocyte antigen workshop, squaw valley, California, July 1995.. Vet Immunol Immunopathol 62:101–143.
    doi: 10.1016/s0165-2427(97)00160-8pubmed: 9638857google scholar: lookup
  59. Wagner B, Glaser A, Hillegas JM, Erb HN, Gold C, Freer H. Monoclonal antibodies to equine IgM improve the sensitivity of West Nile virus-specific IgM detection in horses.. Vet Immunol Immunopathol 122:46–56.
    doi: 10.1016/j.vetimm.2007.10.013pubmed: 18054390google scholar: lookup
  60. Perkins GA, Goodman LB, Wimer C, Freer H, Babasyan S, Wagner B. Maternal T-lymphocytes in equine colostrum express a primarily inflammatory phenotype.. Vet Immunol Immunopathol 161:141–150.
    doi: 10.1016/j.vetimm.2014.07.009pubmed: 25174977google scholar: lookup
  61. Wagner B, Hillegas JM, Babasyan S. Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IGE on subpopulations of IgM and IgG1 B-cells in horses.. Vet Immunol Immunopathol 146:125–134.
    doi: 10.1016/j.vetimm.2012.02.007pubmed: 22405681google scholar: lookup
  62. Wagner B, Goodman LB, Babasyan S, Freer H, Torsteinsdóttir S, Svansson V, Björnsdóttir S, Perkins GA. Antibody and cellular immune responses of naïve mares to repeated vaccination with an Inactivated equine herpesvirus vaccine.. Vaccine 33:5588–5597.
    doi: 10.1016/j.vaccine.2015.09.009pubmed: 26384446google scholar: lookup
  63. Sheoran AS, Timoney JF, Holmes MA, Karzenski SS, Crisman MV. Immunoglobulin isotypes in sera and nasal mucosal secretions and their neonatal transfer and distribution in horses.. Am J Vet Res 61:1099–1105.
    doi: 10.2460/ajvr.2000.61.1099pubmed: 10976743google scholar: lookup

Citations

This article has been cited 6 times.
  1. Pusterla N, Lawton K, Barnum S, Flynn K, Hankin S, Runk D, Mendonsa E, Doherty T. Management of an Equine Herpesvirus-1 Outbreak During a Multi-Week Equestrian Event. Viruses 2025 Apr 24;17(5).
    doi: 10.3390/v17050608pubmed: 40431620google scholar: lookup
  2. Wagner B, Schnabel CL, Rollins A. Increase in Virus-Specific Mucosal Antibodies in the Upper Respiratory Tract Following Intramuscular Vaccination of Previously Exposed Horses Against Equine Herpesvirus Type-1/4. Vaccines (Basel) 2025 Mar 10;13(3).
    doi: 10.3390/vaccines13030290pubmed: 40266191google scholar: lookup
  3. Pusterla N, Lawton K, Barnum S, Ross K, Purcell K. Investigation of an Outbreak of Equine Herpesvirus-1 Myeloencephalopathy in a Population of Aged Working Equids. Viruses 2024 Dec 21;16(12).
    doi: 10.3390/v16121963pubmed: 39772269google scholar: lookup
  4. Holmes CM, Wagner B. Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1. Viruses 2024 Sep 25;16(10).
    doi: 10.3390/v16101514pubmed: 39459849google scholar: lookup
  5. Hu Y, Zhang SY, Sun WC, Feng YR, Gong HR, Ran DL, Zhang BZ, Liu JH. Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity. Viruses 2024 Sep 16;16(9).
    doi: 10.3390/v16091472pubmed: 39339948google scholar: lookup
  6. Holmes CM, Babasyan S, Eady N, Schnabel CL, Wagner B. Immune horses rapidly increase antileukoproteinase and lack type I interferon secretion during mucosal innate immune responses against equine herpesvirus type 1. Microbiol Spectr 2024 Oct 3;12(10):e0109224.
    doi: 10.1128/spectrum.01092-24pubmed: 39162558google scholar: lookup
Subscribe to our newsletter
Join 99,970 horse owners like you who receive our email updates on horse health and nutrition.