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Journal of virology2019; 93(7); e02098-18; doi: 10.1128/JVI.02098-18

Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs.

Abstract: Equine herpesvirus 1 (EHV1) replicates in the respiratory epithelium and disseminates through the body via a cell-associated viremia in leukocytes, despite the presence of neutralizing antibodies. "Hijacked" leukocytes, previously identified as monocytic cells and T lymphocytes, transmit EHV1 to endothelial cells of the endometrium or central nervous system, causing reproductive (abortigenic variants) or neurological (neurological variants) disorders. In the present study, we questioned the potential route of EHV1 infection of T lymphocytes and how EHV1 misuses T lymphocytes as a vehicle to reach the endothelium of the target organs in the absence or presence of immune surveillance. Viral replication was evaluated in activated and quiescent primary T lymphocytes, and the results demonstrated increased infection of activated versus quiescent, CD4 versus CD8, and blood- versus lymph node-derived T cells. Moreover, primarily infected respiratory epithelial cells and circulating monocytic cells efficiently transferred virions to T lymphocytes in the presence of neutralizing antibodies. Albeit T-lymphocytes express all classes of viral proteins early in infection, the expression of viral glycoproteins on their cell surface was restricted. In addition, the release of viral progeny was hampered, resulting in the accumulation of viral nucleocapsids in the T cell nucleus. During contact of infected T lymphocytes with endothelial cells, a late viral protein(s) orchestrates T cell polarization and synapse formation, followed by anterograde dynein-mediated transport and transfer of viral progeny to the engaged cell. This represents a sophisticated but efficient immune evasion strategy to allow transfer of progeny virus from T lymphocytes to adjacent target cells. These results demonstrate that T lymphocytes are susceptible to EHV1 infection and that cell-cell contact transmits infectious virus to and from T lymphocytes. Equine herpesvirus 1 (EHV1) is an ancestral alphaherpesvirus that is related to herpes simplex virus 1 and causes respiratory, reproductive, and neurological disorders in Equidae. EHV1 is indisputably a master at exploiting leukocytes to reach its target organs, accordingly evading the host immunity. However, the role of T lymphocytes in cell-associated viremia remains poorly understood. Here we show that activated T lymphocytes efficiently become infected and support viral replication despite the presence of protective immunity. We demonstrate a restricted expression of viral proteins on the surfaces of infected T cells, which prevents immune recognition. In addition, we indicate a hampered release of progeny, which results in the accumulation of nucleocapsids in the T cell nucleus. Upon engagement with the target endothelium, late viral proteins orchestrate viral synapse formation and viral transfer to the contact cell. Our findings have significant implications for the understanding of EHV1 pathogenesis, which is essential for developing innovative therapies to prevent the devastating clinical symptoms of infection.
Copyright © 2019 Poelaert et al.
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Publication Date: 2019-03-21 PubMed ID: 30651370PubMed Central: PMC6430527DOI: 10.1128/JVI.02098-18Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study focuses on how Equine herpesvirus 1 (EHV1), a disease-causing agent in horses, leverages T lymphocytes (a type of white blood cell) to reach its target organs, causing reproductive or neurological disorders.

Methodology and Key Findings

The researchers examined how the EHV1 infection progresses in T lymphocytes under various conditions:

  • Viral replication was studied in different states of primary T lymphocytes – both activated (responsive) and quiescent (inactive).
  • It was observed that the virus infected a higher number of activated, CD4, and blood-derived T cells compared to quiescent, CD8, and lymph-node derived T cells.
  • Notably, the EHV1 virus was discovered to transfer efficiently from primarily infected respiratory epithelial cells and circulating monocytic cells (another type of white blood cell) to T lymphocytes, even in the presence of neutralizing antibodies.
  • In infected T lymphocytes, while all classes of viral proteins were expressed early, the surface expression of viral glycoproteins was limited.
  • The release of new viruses from the T lymphocytes was found to be limited, causing an accumulation of viral elements in the T cell nucleus.

Interaction of Infected T Lymphocytes with Endothelial Cells

When infected T lymphocytes contact endothelial cells (that line the interior of blood vessels), some interesting processes were observed:

  • A late viral protein helps in organizing cell polarization and synapse formation – a connection between the T lymphocyte and the endothelial cell.
  • This connection enables the forward transport (mediated by a motor protein called dynein) and transfer of new viruses to the endothelial cell.

Conclusion and Implications

The study demonstrated that T lymphocytes are susceptible to EHV1 infection and can transfer the virus to other cells through direct contact. It highlighted a sophisticated immune evasion tactic used by the virus, where restricted expression of viral proteins on infected T cells prevents immune recognition. The study’s findings have significant implications for understanding EHV1’s pathogenesis and potentially developing innovative therapies to prevent the severe clinical symptoms of this infection.

Cite This Article

APA
Poelaert KCK, Van Cleemput J, Laval K, Favoreel HW, Couck L, Van den Broeck W, Azab W, Nauwynck HJ. (2019). Equine Herpesvirus 1 Bridles T Lymphocytes To Reach Its Target Organs. J Virol, 93(7), e02098-18. https://doi.org/10.1128/JVI.02098-18

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 93
Issue: 7
PII: e02098-18

Researcher Affiliations

Poelaert, Katrien C K
  • Department of Virology, Immunology and Parasitology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Van Cleemput, Jolien
  • Department of Virology, Immunology and Parasitology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Laval, Kathlyn
  • Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Favoreel, Herman W
  • Department of Virology, Immunology and Parasitology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Couck, Liesbeth
  • Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Van den Broeck, Wim
  • Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Azab, Walid
  • Institut fur Virologie, Zentrum fur Infektionsmedezin, Freie Universitat Berlin, Berlin, Germany.
Nauwynck, Hans J
  • Department of Virology, Immunology and Parasitology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium hans.nauwynck@ugent.be.

MeSH Terms

  • Animals
  • Cells, Cultured
  • Endothelial Cells / immunology
  • Endothelial Cells / virology
  • Epithelial Cells / immunology
  • Epithelial Cells / virology
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Equid / immunology
  • Horse Diseases / immunology
  • Horse Diseases / virology
  • Horses / immunology
  • Horses / virology
  • Immune Evasion / immunology
  • Monocytes / immunology
  • Monocytes / virology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / virology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Viral Proteins / immunology
  • Viremia / immunology
  • Viremia / virology
  • Virus Replication / immunology

References

This article includes 97 references
  1. Roizman B. 1996. Herpesviridae, p 2221–2230. In Fields BN, Knipe DM, Howley PM (ed), Fields virology, 3rd ed Lippincott-Raven Publishers; Philadelphia, PA.
  2. Karlin S, Mocarski ES, Schachtel GA. Molecular evolution of herpesviruses: genomic and protein sequence comparisons.. J Virol 1994 Mar;68(3):1886-902.
    pmc: PMC236651pubmed: 8107249doi: 10.1128/jvi.68.3.1886-1902.1994google scholar: lookup
  3. Lunn DP, Davis-Poynter N, Flaminio MJ, Horohov DW, Osterrieder K, Pusterla N, Townsend HG. Equine herpesvirus-1 consensus statement.. J Vet Intern Med 2009 May-Jun;23(3):450-61.
    doi: 10.1111/j.1939-1676.2009.0304.xpubmed: 19645832google scholar: lookup
  4. Edington N, Welch HM, Griffiths L. The prevalence of latent Equid herpesviruses in the tissues of 40 abattoir horses.. Equine Vet J 1994 Mar;26(2):140-2.
    doi: 10.1111/j.2042-3306.1994.tb04353.xpubmed: 8575377google scholar: lookup
  5. Allen G, Kydd J, Slater J, Smith K. 2004. Equid herpesvirus-1 (EHV-1) and -4 (EHV-4) infections, p 829–859. In Coetzer J, Tustin R (ed), Infectious diseases of livestock, 2nd ed Oxford Press; Cape Town, South Africa.
  6. 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 2010 Aug;91(Pt 8):2019-2028.
    doi: 10.1099/vir.0.019257-0pubmed: 20427565google scholar: lookup
  7. Gryspeerdt AC, Vandekerckhove AP, Garré B, Barbé F, Van de Walle GR, Nauwynck HJ. Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses.. Vet Microbiol 2010 May 19;142(3-4):242-53.
    doi: 10.1016/j.vetmic.2009.10.015pubmed: 19926232google scholar: lookup
  8. van Der Meulen KM, Nauwynck HJ, Bí¶®rt W, Pensaert MB. Replication of equine herpesvirus type 1 in freshly isolated equine peripheral blood mononuclear cells and changes in susceptibility following mitogen stimulation.. J Gen Virol 2000 Jan;81(Pt 1):21-5.
    doi: 10.1099/0022-1317-81-1-21pubmed: 10640538google scholar: lookup
  9. Laval K, Favoreel HW, Nauwynck HJ. Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases.. J Gen Virol 2015 Jan;96(Pt 1):118-130.
    doi: 10.1099/vir.0.067363-0pubmed: 25239765google scholar: lookup
  10. Edington N, Bridges CG, Patel JR. Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: equine stroke.. Arch Virol 1986;90(1-2):111-24.
    doi: 10.1007/BF01314149pubmed: 3015074google scholar: lookup
  11. 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 1991 May;104(4):379-87.
    doi: 10.1016/S0021-9975(08)80148-Xpubmed: 1651960google scholar: lookup
  12. 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 2006 May-Jun;20(3):601-7.
    pubmed: 16734096doi: 10.1892/0891-6640(2006)20[601:ehtami]2.0.co;2google scholar: lookup
  13. Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N. Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.. J Virol 2006 Apr;80(8):4047-60.
    doi: 10.1128/JVI.80.8.4047-4060.2006pmc: PMC1440451pubmed: 16571821google scholar: lookup
  14. 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 2017 Feb 27;48(1):14.
    doi: 10.1186/s13567-017-0419-4pmc: PMC5327560pubmed: 28241864google scholar: lookup
  15. Laval K, Van Cleemput J, Poelaert KC, Brown IK, Nauwynck HJ. Replication of neurovirulent equine herpesvirus type 1 (EHV-1) in CD172a(+) monocytic cells.. Comp Immunol Microbiol Infect Dis 2017 Feb;50:58-62.
    doi: 10.1016/j.cimid.2016.11.006pubmed: 28131380google scholar: lookup
  16. Topham DJ, Reilly EC. Tissue-Resident Memory CD8(+) T Cells: From Phenotype to Function.. Front Immunol 2018;9:515.
    doi: 10.3389/fimmu.2018.00515pmc: PMC5879098pubmed: 29632527google scholar: lookup
  17. Park CO, Kupper TS. The emerging role of resident memory T cells in protective immunity and inflammatory disease.. Nat Med 2015 Jul;21(7):688-97.
    doi: 10.1038/nm.3883pmc: PMC4640452pubmed: 26121195google scholar: lookup
  18. Kydd JH, Hannant D, Mumford JA. Residence and recruitment of leucocytes to the equine lung after EHV-1 infection.. Vet Immunol Immunopathol 1996 Jun 15;52(1-2):15-26.
    doi: 10.1016/0165-2427(95)05533-9pubmed: 8807773google scholar: lookup
  19. Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells.. Nat Immunol 2016 May 19;17(6):618-25.
    doi: 10.1038/ni.3466pmc: PMC5006394pubmed: 27196520google scholar: lookup
  20. Breathnach CC, Soboll G, Suresh M, Lunn DP. Equine herpesvirus-1 infection induces IFN-gamma production by equine T lymphocyte subsets.. Vet Immunol Immunopathol 2005 Feb 10;103(3-4):207-15.
    doi: 10.1016/j.vetimm.2004.09.024pubmed: 15621307google scholar: lookup
  21. Allen G, Yeargan M, Costa LR, Cross R. Major histocompatibility complex class I-restricted cytotoxic T-lymphocyte responses in horses infected with equine herpesvirus 1.. J Virol 1995 Jan;69(1):606-12.
    pmc: PMC188619pubmed: 7983765doi: 10.1128/jvi.69.1.606-612.1995google scholar: lookup
  22. Kydd JH, Smith KC, Hannant D, Livesay GJ, Mumford JA. Distribution of equid herpesvirus-1 (EHV-1) in respiratory tract associated lymphoid tissue: implications for cellular immunity.. Equine Vet J 1994 Nov;26(6):470-3.
    doi: 10.1111/j.2042-3306.1994.tb04052.xpubmed: 7889921google scholar: lookup
  23. Slater JD, Borchers K, Thackray AM, Field HJ. The trigeminal ganglion is a location for equine herpesvirus 1 latency and reactivation in the horse.. J Gen Virol 1994 Aug;75 ( Pt 8):2007-16.
    doi: 10.1099/0022-1317-75-8-2007pubmed: 8046404google scholar: lookup
  24. Chesters PM, Allsop R, Purewal A, Edington N. Detection of latency-associated transcripts of equid herpesvirus 1 in equine leukocytes but not in trigeminal ganglia.. J Virol 1997 May;71(5):3437-43.
    pmc: PMC191489pubmed: 9094614doi: 10.1128/jvi.71.5.3437-3443.1997google scholar: lookup
  25. Kannan Y, Wilson MS. TEC and MAPK Kinase Signalling Pathways in T helper (T(H)) cell Development, T(H)2 Differentiation and Allergic Asthma.. J Clin Cell Immunol 2012;Suppl 12:11.
    pmc: PMC3792371pubmed: 24116341doi: 10.4172/2155-9899.s12-011google scholar: lookup
  26. Pross S. 2007. Major histocompatibility complex, p 1–7. In Enna SJ, Bylund DB (ed), xPharm: the comprehensive pharmacology reference. Elsevier; New York, NY.
  27. Verbsky JW, Chatila TA. 2014. Chapter 23—immune dysregulation leading to chronic autoimmunity, p 497–516. In Sullivan KE, Stiehm ER (ed), Stiehm’s immune deficiencies. Academic Press; Amsterdam, Netherlands.
  28. Geginat J, Sallusto F, Lanzavecchia A. Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells.. J Exp Med 2001 Dec 17;194(12):1711-9.
    doi: 10.1084/jem.194.12.1711pmc: PMC2193568pubmed: 11748273google scholar: lookup
  29. Bouayyad A, Menezes J. Comparative study of herpes simplex virus receptor expression on human lymphoid cells.. Virology 1990 Dec;179(2):905-10.
    doi: 10.1016/0042-6822(90)90166-Opubmed: 2173267google scholar: lookup
  30. Aubert M, Yoon M, Sloan DD, Spear PG, Jerome KR. The virological synapse facilitates herpes simplex virus entry into T cells.. J Virol 2009 Jun;83(12):6171-83.
    doi: 10.1128/JVI.02163-08pmc: PMC2687377pubmed: 19339346google scholar: lookup
  31. Eskra L, Splitter GA. Bovine herpesvirus-1 infects activated CD4+ lymphocytes.. J Gen Virol 1997 Sep;78 ( Pt 9):2159-66.
    doi: 10.1099/0022-1317-78-9-2159pubmed: 9292002google scholar: lookup
  32. Thomson GR, Mumford JA. In vitro stimulation of foal lymphocytes with equid herpesvirus 1.. Res Vet Sci 1977 May;22(3):347-52.
    pubmed: 195321
  33. Ku CC, Padilla JA, Grose C, Butcher EC, Arvin AM. Tropism of varicella-zoster virus for human tonsillar CD4(+) T lymphocytes that express activation, memory, and skin homing markers.. J Virol 2002 Nov;76(22):11425-33.
    doi: 10.1128/JVI.76.22.11425-11433.2002pmc: PMC136789pubmed: 12388703google scholar: lookup
  34. Smith DJ, Hamblin AS, Edington N. Infection of endothelial cells with equine herpesvirus-1 (EHV-1) occurs where there is activation of putative adhesion molecules: a mechanism for transfer of virus.. Equine Vet J 2001 Mar;33(2):138-42.
    pubmed: 11266062doi: 10.1111/j.2042-3306.2001.tb00591.xgoogle scholar: lookup
  35. Goehring LS, Hussey GS, Ashton LV, Schenkel AR, Lunn DP. Infection of central nervous system endothelial cells by cell-associated EHV-1.. Vet Microbiol 2011 Mar 24;148(2-4):389-95.
    doi: 10.1016/j.vetmic.2010.08.030pubmed: 20884134google scholar: lookup
  36. Harel-Bellan A, Bertoglio J, Quillet A, Marchiol C, Wakasugi H, Mishall Z, Fradelizi D. Interleukin 2 (IL 2) up-regulates its own receptor on a subset of human unprimed peripheral blood lymphocytes and triggers their proliferation.. J Immunol 1986 Apr 1;136(7):2463-9.
    pubmed: 3005412
  37. Depper JM, Leonard WJ, Drogula C, Krönke M, Waldmann TA, Greene WC. Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene.. Proc Natl Acad Sci U S A 1985 Jun;82(12):4230-4.
    doi: 10.1073/pnas.82.12.4230pmc: PMC397970pubmed: 2987968google scholar: lookup
  38. Shipkova M, Wieland E. Surface markers of lymphocyte activation and markers of cell proliferation.. Clin Chim Acta 2012 Sep 8;413(17-18):1338-49.
    doi: 10.1016/j.cca.2011.11.006pubmed: 22120733google scholar: lookup
  39. Paul WE, Seder RA. Lymphocyte responses and cytokines.. Cell 1994 Jan 28;76(2):241-51.
    doi: 10.1016/0092-8674(94)90332-8pubmed: 7904900google scholar: lookup
  40. Roh KH, Lillemeier BF, Wang F, Davis MM. The coreceptor CD4 is expressed in distinct nanoclusters and does not colocalize with T-cell receptor and active protein tyrosine kinase p56lck.. Proc Natl Acad Sci U S A 2015 Mar 31;112(13):E1604-13.
    doi: 10.1073/pnas.1503532112pmc: PMC4386407pubmed: 25829544google scholar: lookup
  41. Jolly C, Welsch S, Michor S, Sattentau QJ. The regulated secretory pathway in CD4(+) T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse.. PLoS Pathog 2011 Sep;7(9):e1002226.
    doi: 10.1371/journal.ppat.1002226pmc: PMC3164651pubmed: 21909273google scholar: lookup
  42. Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber JN, Griffiths GM, Tanaka Y, Osame M, Bangham CR. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton.. Science 2003 Mar 14;299(5613):1713-6.
    doi: 10.1126/science.1080115pubmed: 12589003google scholar: lookup
  43. Barnard AL, Igakura T, Tanaka Y, Taylor GP, Bangham CR. Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes.. Blood 2005 Aug 1;106(3):988-95.
    doi: 10.1182/blood-2004-07-2850pubmed: 15831709google scholar: lookup
  44. Combs J, Kim SJ, Tan S, Ligon LA, Holzbaur EL, Kuhn J, Poenie M. Recruitment of dynein to the Jurkat immunological synapse.. Proc Natl Acad Sci U S A 2006 Oct 3;103(40):14883-8.
    doi: 10.1073/pnas.0600914103pmc: PMC1595445pubmed: 16990435google scholar: lookup
  45. Kupfer A, Swain SL, Singer SJ. The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells.. J Exp Med 1987 Jun 1;165(6):1565-80.
    doi: 10.1084/jem.165.6.1565pmc: PMC2188362pubmed: 2953845google scholar: lookup
  46. Kupfer A, Dennert G, Singer SJ. Polarization of the Golgi apparatus and the microtubule-organizing center within cloned natural killer cells bound to their targets.. Proc Natl Acad Sci U S A 1983 Dec;80(23):7224-8.
    doi: 10.1073/pnas.80.23.7224pmc: PMC390027pubmed: 6359165google scholar: lookup
  47. Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM. Centrosome polarization delivers secretory granules to the immunological synapse.. Nature 2006 Sep 28;443(7110):462-5.
    doi: 10.1038/nature05071pubmed: 17006514google scholar: lookup
  48. Neeson PJ, Thurlow PJ, Jamieson GP. Characterization of activated lymphocyte-tumor cell adhesion.. J Leukoc Biol 2000 Jun;67(6):847-55.
    doi: 10.1002/jlb.67.6.847pubmed: 10857858google scholar: lookup
  49. Starling S, Jolly C. LFA-1 Engagement Triggers T Cell Polarization at the HIV-1 Virological Synapse.. J Virol 2016 Nov 1;90(21):9841-9854.
    doi: 10.1128/JVI.01152-16pmc: PMC5068534pubmed: 27558417google scholar: lookup
  50. Gibbons BH, Gibbons IR. Vanadate-sensitized cleavage of dynein heavy chains by 365-nm irradiation of demembranated sperm flagella and its effect on the flagellar motility.. J Biol Chem 1987 Jun 15;262(17):8354-9.
    pubmed: 2954952
  51. Stein WD, Litman T. 2015. Chapter 6—primary active transport systems, p 247–328. In Stein WD, Litman T (ed), Channels, carriers, and pumps, 2nd ed Elsevier; London, United Kingdom.
  52. Moores CA. Dynein: a force (generation mechanism) to be reckoned with.. Structure 2012 Oct 10;20(10):1611-2.
    doi: 10.1016/j.str.2012.09.002pubmed: 23063004google scholar: lookup
  53. Schaap A, Fortin JF, Sommer M, Zerboni L, Stamatis S, Ku CC, Nolan GP, Arvin AM. T-cell tropism and the role of ORF66 protein in pathogenesis of varicella-zoster virus infection.. J Virol 2005 Oct;79(20):12921-33.
    doi: 10.1128/JVI.79.20.12921-12933.2005pmc: PMC1235817pubmed: 16188994google scholar: lookup
  54. Sloan DD, Zahariadis G, Posavad CM, Pate NT, Kussick SJ, Jerome KR. CTL are inactivated by herpes simplex virus-infected cells expressing a viral protein kinase.. J Immunol 2003 Dec 15;171(12):6733-41.
    doi: 10.4049/jimmunol.171.12.6733pubmed: 14662877google scholar: lookup
  55. Ku CC, Zerboni L, Ito H, Graham BS, Wallace M, Arvin AM. Varicella-zoster virus transfer to skin by T Cells and modulation of viral replication by epidermal cell interferon-alpha.. J Exp Med 2004 Oct 4;200(7):917-25.
    doi: 10.1084/jem.20040634pmc: PMC2213285pubmed: 15452178google scholar: lookup
  56. 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 2012 Aug;193(2):576-8.
    doi: 10.1016/j.tvjl.2012.01.022pubmed: 22425309google scholar: lookup
  57. Gleeson LJ, Coggins L. Response of pregnant mares to equine herpesvirus 1 (EHV1).. Cornell Vet 1980 Oct;70(4):391-400.
    pubmed: 6257449
  58. Mackay CR, Kimpton WG, Brandon MR, Cahill RN. Lymphocyte subsets show marked differences in their distribution between blood and the afferent and efferent lymph of peripheral lymph nodes.. J Exp Med 1988 Jun 1;167(6):1755-65.
    doi: 10.1084/jem.167.6.1755pmc: PMC2189690pubmed: 3290379google scholar: lookup
  59. Shin H, Iwasaki A. Tissue-resident memory T cells.. Immunol Rev 2013 Sep;255(1):165-81.
    doi: 10.1111/imr.12087pmc: PMC3748618pubmed: 23947354google scholar: lookup
  60. Goodman LB, Loregian A, Perkins GA, Nugent J, Buckles EL, Mercorelli B, Kydd JH, Palù G, Smith KC, Osterrieder N, Davis-Poynter N. A point mutation in a herpesvirus polymerase determines neuropathogenicity.. PLoS Pathog 2007 Nov;3(11):e160.
    doi: 10.1371/journal.ppat.0030160pmc: PMC2065875pubmed: 17997600google scholar: lookup
  61. Winkler MT, Doster A, Jones C. Bovine herpesvirus 1 can infect CD4(+) T lymphocytes and induce programmed cell death during acute infection of cattle.. J Virol 1999 Oct;73(10):8657-68.
    pmc: PMC112886pubmed: 10482619doi: 10.1128/jvi.73.10.8657-8668.1999google scholar: lookup
  62. Takahashi K, Sonoda S, Higashi K, Kondo T, Takahashi H, Takahashi M, Yamanishi K. Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus.. J Virol 1989 Jul;63(7):3161-3.
    pmc: PMC250875pubmed: 2542623doi: 10.1128/jvi.63.7.3161-3163.1989google scholar: lookup
  63. Lusso P, Secchiero P, Crowley RW, Garzino-Demo A, Berneman ZN, Gallo RC. CD4 is a critical component of the receptor for human herpesvirus 7: interference with human immunodeficiency virus.. Proc Natl Acad Sci U S A 1994 Apr 26;91(9):3872-6.
    doi: 10.1073/pnas.91.9.3872pmc: PMC43684pubmed: 7909607google scholar: lookup
  64. Overmann J. 2017. Leukocytes, p 119–125. In Pusterla N, Higgins J (ed), Interpretation of equine laboratory diagnostics. John Wiley & Sons, Inc; Hoboken, NJ.
  65. Manickan E, Rouse RJ, Yu Z, Wire WS, Rouse BT. Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes.. J Immunol 1995 Jul 1;155(1):259-65.
    pubmed: 7602102
  66. Milligan GN, Bernstein DI. Analysis of herpes simplex virus-specific T cells in the murine female genital tract following genital infection with herpes simplex virus type 2.. Virology 1995 Oct 1;212(2):481-9.
    doi: 10.1006/viro.1995.1506pubmed: 7571418google scholar: lookup
  67. Rathmell JC, Vander Heiden MG, Harris MH, Frauwirth KA, Thompson CB. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability.. Mol Cell 2000 Sep;6(3):683-92.
    doi: 10.1016/S1097-2765(00)00066-6pubmed: 11030347google scholar: lookup
  68. Frauwirth KA, Thompson CB. Regulation of T lymphocyte metabolism.. J Immunol 2004 Apr 15;172(8):4661-5.
    doi: 10.4049/jimmunol.172.8.4661pubmed: 15067038google scholar: lookup
  69. Wilsterman S, Soboll-Hussey G, Lunn DP, Ashton LV, Callan RJ, Hussey SB, Rao S, Goehring LS. Equine herpesvirus-1 infected peripheral blood mononuclear cell subpopulations during viremia.. Vet Microbiol 2011 Apr 21;149(1-2):40-7.
    doi: 10.1016/j.vetmic.2010.10.004pubmed: 21093993google scholar: lookup
  70. Favoreel HW, Nauwynck HJ, Van Oostveldt P, Mettenleiter TC, Pensaert MB. Antibody-induced and cytoskeleton-mediated redistribution and shedding of viral glycoproteins, expressed on pseudorabies virus-infected cells.. J Virol 1997 Nov;71(11):8254-61.
    pmc: PMC192283pubmed: 9343177doi: 10.1128/jvi.71.11.8254-8261.1997google scholar: lookup
  71. Ben-Porat T, DeMarchi J, Pendrys J, Veach RA, Kaplan AS. Proteins specified by the short unique region of the genome of pseudorabies virus play a role in the release of virions from certain cells.. J Virol 1986 Jan;57(1):191-6.
    pmc: PMC252714pubmed: 3001344doi: 10.1128/jvi.57.1.191-196.1986google scholar: lookup
  72. Favoreel HW, Nauwynck HJ, Halewyck HM, Van Oostveldt P, Mettenleiter TC, Pensaert MB. Antibody-induced endocytosis of viral glycoproteins and major histocompatibility complex class I on pseudorabies virus-infected monocytes.. J Gen Virol 1999 May;80 ( Pt 5):1283-1291.
    doi: 10.1099/0022-1317-80-5-1283pubmed: 10355775google scholar: lookup
  73. Reichelt M, Wang L, Sommer M, Perrino J, Nour AM, Sen N, Baiker A, Zerboni L, Arvin AM. Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.. PLoS Pathog 2011 Feb 3;7(2):e1001266.
    doi: 10.1371/journal.ppat.1001266pmc: PMC3033373pubmed: 21304940google scholar: lookup
  74. Spiesschaert B, Goldenbogen B, Taferner S, Schade M, Mahmoud M, Klipp E, Osterrieder N, Azab W. Role of gB and pUS3 in Equine Herpesvirus 1 Transfer between Peripheral Blood Mononuclear Cells and Endothelial Cells: a Dynamic In Vitro Model.. J Virol 2015 Dec;89(23):11899-908.
    doi: 10.1128/JVI.01809-15pmc: PMC4645325pubmed: 26378176google scholar: lookup
  75. Reynolds AE, Liang L, Baines JD. Conformational changes in the nuclear lamina induced by herpes simplex virus type 1 require genes U(L)31 and U(L)34.. J Virol 2004 Jun;78(11):5564-75.
    doi: 10.1128/JVI.78.11.5564-5575.2004pmc: PMC415827pubmed: 15140953google scholar: lookup
  76. Bjerke SL, Roller RJ. Roles for herpes simplex virus type 1 UL34 and US3 proteins in disrupting the nuclear lamina during herpes simplex virus type 1 egress.. Virology 2006 Apr 10;347(2):261-76.
    doi: 10.1016/j.virol.2005.11.053pmc: PMC2993110pubmed: 16427676google scholar: lookup
  77. Mou F, Forest T, Baines JD. US3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin A/C in infected cells.. J Virol 2007 Jun;81(12):6459-70.
    doi: 10.1128/JVI.00380-07pmc: PMC1900093pubmed: 17428859google scholar: lookup
  78. Proft A, Spiesschaert B, Izume S, Taferner S, Lehmann MJ, Azab W. The Role of the Equine Herpesvirus Type 1 (EHV-1) US3-Encoded Protein Kinase in Actin Reorganization and Nuclear Egress.. Viruses 2016 Oct 12;8(10).
    pmc: PMC5086611pubmed: 27754319doi: 10.3390/v8100275google scholar: lookup
  79. Jolly C, Sattentau QJ. Retroviral spread by induction of virological synapses.. Traffic 2004 Sep;5(9):643-50.
    doi: 10.1111/j.1600-0854.2004.00209.xpubmed: 15296489google scholar: lookup
  80. Mages J, Freimüller K, Lang R, Hatzopoulos AK, Guggemoos S, Koszinowski UH, Adler H. Proteins of the secretory pathway govern virus productivity during lytic gammaherpesvirus infection.. J Cell Mol Med 2008 Oct;12(5B):1974-89.
    doi: 10.1111/j.1582-4934.2008.00235.xpmc: PMC2673020pubmed: 18194452google scholar: lookup
  81. van der Meulen K, Vercauteren G, Nauwynck H, Pensaert M. A local epidemic of equine herpesvirus 1-induced neurological disorders in Belgium. Vlaams Diergeneeskundig Tijdschrift 2003;72:366–372.
  82. Van de Walle GR, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N. A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease.. J Infect Dis 2009 Jul 1;200(1):20-5.
    doi: 10.1086/599316pubmed: 19456260google scholar: lookup
  83. Garré B, Gryspeerdt A, Croubels S, De Backer P, Nauwynck H. Evaluation of orally administered valacyclovir in experimentally EHV1-infected ponies.. Vet Microbiol 2009 Mar 30;135(3-4):214-21.
    doi: 10.1016/j.vetmic.2008.09.062pubmed: 18986780google scholar: lookup
  84. Azab W, Lehmann MJ, Osterrieder N. Glycoprotein H and α4β1 integrins determine the entry pathway of alphaherpesviruses.. J Virol 2013 May;87(10):5937-48.
    doi: 10.1128/JVI.03522-12pmc: PMC3648174pubmed: 23514881google scholar: lookup
  85. RECZKO E, MAYR A. [ON THE FINE STRUCTURE OF A VIRUS OF THE HERPES GROUP ISOLATED FROM HORSES (SHORT REPORT)].. Arch Gesamte Virusforsch 1963 Aug 26;13:591-3.
    doi: 10.1007/BF01267802pubmed: 14078849google scholar: lookup
  86. Vandekerckhove AP, Glorieux S, Gryspeerdt AC, Steukers L, Van Doorsselaere J, Osterrieder N, Van de Walle GR, Nauwynck HJ. Equine alphaherpesviruses (EHV-1 and EHV-4) differ in their efficiency to infect mononuclear cells during early steps of infection in nasal mucosal explants.. Vet Microbiol 2011 Aug 26;152(1-2):21-8.
    doi: 10.1016/j.vetmic.2011.03.038pubmed: 21536394google scholar: lookup
  87. Matheu MP, Cahalan MD. Isolation of CD4+ T cells from mouse lymph nodes using Miltenyi MACS purification.. J Vis Exp 2007;(9):409.
    pmc: PMC2566326pubmed: 18989449doi: 10.3791/409google scholar: lookup
  88. Laval K, Favoreel HW, Poelaert KC, Van Cleemput J, Nauwynck HJ. Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.. J Virol 2015 Nov;89(21):10912-23.
    doi: 10.1128/JVI.01589-15pmc: PMC4621108pubmed: 26292328google scholar: lookup
  89. Quintana AM, Landolt GA, Annis KM, Hussey GS. Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model.. Vet Immunol Immunopathol 2011 Apr 15;140(3-4):226-36.
    doi: 10.1016/j.vetimm.2010.12.008pubmed: 21292331google scholar: lookup
  90. Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Epidemiol 1938;27:493–497.
    doi: 10.1093/oxfordjournals.aje.a118408google scholar: lookup
  91. Burkhardt JK, Echeverri CJ, Nilsson T, Vallee RB. Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution.. J Cell Biol 1997 Oct 20;139(2):469-84.
    doi: 10.1083/jcb.139.2.469pmc: PMC2139801pubmed: 9334349google scholar: lookup
  92. Döhner K, Wolfstein A, Prank U, Echeverri C, Dujardin D, Vallee R, Sodeik B. Function of dynein and dynactin in herpes simplex virus capsid transport.. Mol Biol Cell 2002 Aug;13(8):2795-809.
    doi: 10.1091/mbc.01-07-0348pmc: PMC117943pubmed: 12181347google scholar: lookup
  93. Honess RW, Watson DH. Herpes simplex virus resistance and sensitivity to phosphonoacetic acid.. J Virol 1977 Feb;21(2):584-600.
    pmc: PMC353861pubmed: 189089doi: 10.1128/jvi.21.2.584-600.1977google scholar: lookup
  94. Smith RH, Zhao Y, O'Callaghan DJ. The equine herpesvirus type 1 immediate-early gene product contains an acidic transcriptional activation domain.. Virology 1994 Aug 1;202(2):760-70.
    doi: 10.1006/viro.1994.1398pubmed: 8030239google scholar: lookup
  95. Jang HK, Albrecht RA, Buczynski KA, Kim SK, Derbigny WA, O'Callaghan DJ. Mapping the sequences that mediate interaction of the equine herpesvirus 1 immediate-early protein and human TFIIB.. J Virol 2001 Nov;75(21):10219-30.
    doi: 10.1128/JVI.75.21.10219-10230.2001pmc: PMC114596pubmed: 11581390google scholar: lookup
  96. 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 Jun 15;157(3-4):333-44.
    doi: 10.1016/j.vetmic.2012.01.014pubmed: 22306037google scholar: lookup
  97. Pulecio J, Petrovic J, Prete F, Chiaruttini G, Lennon-Dumenil AM, Desdouets C, Gasman S, Burrone OR, Benvenuti F. Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse.. J Exp Med 2010 Nov 22;207(12):2719-32.
    doi: 10.1084/jem.20100007pmc: PMC2989776pubmed: 21059854google scholar: lookup

Citations

This article has been cited 15 times.
  1. Tang X, Sun P, Wang H, Cao J, Xing J, Sheng X, Chi H, Zhan W. Zinc Finger Protein BCL11A Contributes to the Abortive Infection of Hirame novirhabdovirus (HIRRV) in B Lymphocytes of Flounder (Paralichthys olivaceus). J Virol 2022 Dec 21;96(24):e0147022.
    doi: 10.1128/jvi.01470-22pubmed: 36448803google scholar: lookup
  2. Thieulent CJ, Sutton G, Toquet MP, Fremaux S, Hue E, Fortier C, Pléau A, Deslis A, Abrioux S, Guitton E, Pronost S, Paillot R. Oral Administration of Valganciclovir Reduces Clinical Signs, Virus Shedding and Cell-Associated Viremia in Ponies Experimentally Infected with the Equid Herpesvirus-1 C(2254) Variant. Pathogens 2022 May 4;11(5).
    doi: 10.3390/pathogens11050539pubmed: 35631060google scholar: lookup
  3. Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G. A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1. Front Vet Sci 2021;8:674850.
    doi: 10.3389/fvets.2021.674850pubmed: 34179166google scholar: lookup
  4. Yuan C, Li Y, Zhang E, Jin Y, Yang Q. The Mechanism of PEDV-Carrying CD3(+) T Cells Migrate into the Intestinal Mucosa of Neonatal Piglets. Viruses 2021 Mar 12;13(3).
    doi: 10.3390/v13030469pubmed: 33809123google scholar: lookup
  5. Laval K, Poelaert KCK, Van Cleemput J, Zhao J, Vandekerckhove AP, Gryspeerdt AC, Garré B, van der Meulen K, Baghi HB, Dubale HN, Zarak I, Van Crombrugge E, Nauwynck HJ. The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1. Front Microbiol 2021;12:662686.
    doi: 10.3389/fmicb.2021.662686pubmed: 33746936google scholar: lookup
  6. 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 2021 Jan 7;10(1).
    doi: 10.3390/pathogens10010043pubmed: 33430330google scholar: lookup
  7. Giessler KS, Samoilowa S, Soboll Hussey G, Kiupel M, Matiasek K, Sledge DG, Liesche F, Schlegel J, Fux R, Goehring LS. Viral Load and Cell Tropism During Early Latent Equid Herpesvirus 1 Infection Differ Over Time in Lymphoid and Neural Tissue Samples From Experimentally Infected Horses. Front Vet Sci 2020;7:621.
    doi: 10.3389/fvets.2020.00621pubmed: 33102556google scholar: lookup
  8. Sutton G, Thieulent C, Fortier C, Hue ES, Marcillaud-Pitel C, Pléau A, Deslis A, Guitton E, Paillot R, Pronost S. Identification of a New Equid Herpesvirus 1 DNA Polymerase (ORF30) Genotype with the Isolation of a C(2254)/H(752) Strain in French Horses Showing no Major Impact on the Strain Behaviour. Viruses 2020 Oct 13;12(10).
    doi: 10.3390/v12101160pubmed: 33066315google scholar: lookup
  9. Pavulraj S, Kamel M, Stephanowitz H, Liu F, Plendl J, Osterrieder N, Azab W. Equine Herpesvirus Type 1 Modulates Cytokine and Chemokine Profiles of Mononuclear Cells for Efficient Dissemination to Target Organs. Viruses 2020 Sep 8;12(9).
    doi: 10.3390/v12090999pubmed: 32911663google scholar: lookup
  10. Poelaert KCK, Van Cleemput J, Laval K, Descamps S, Favoreel HW, Nauwynck HJ. Beyond Gut Instinct: Metabolic Short-Chain Fatty Acids Moderate the Pathogenesis of Alphaherpesviruses. Front Microbiol 2019;10:723.
    doi: 10.3389/fmicb.2019.00723pubmed: 31024501google scholar: lookup
  11. de la Cuesta-Torrado M, Vitale V, Velloso Alvarez A, Neira-Egea P, Diss C, Cuervo-Arango J. The Effect of Vaccination Status on Total Lymphocyte Count in Horses Affected by Equine Herpes Virus-1 Myeloencephalopathy. Animals (Basel) 2025 Apr 1;15(7).
    doi: 10.3390/ani15071019pubmed: 40218411google scholar: lookup
  12. 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
  13. Van Crombrugge E, Ren X, Glorieux S, Zarak I, Van den Broeck W, Bachert C, Zhang N, Van Zele T, Kim D, Smith GA, Laval K, Nauwynck H. The alphaherpesvirus gE/gI glycoprotein complex and proteases jointly orchestrate invasion across the host's upper respiratory epithelial barrier. mBio 2024 Nov 13;15(11):e0187324.
    doi: 10.1128/mbio.01873-24pubmed: 39382295google scholar: lookup
  14. Hassanien RT, Thieulent CJ, Carossino M, Li G, Balasuriya UBR. Modulation of Equid Herpesvirus-1 Replication Dynamics In Vitro Using CRISPR/Cas9-Assisted Genome Editing. Viruses 2024 Mar 6;16(3).
    doi: 10.3390/v16030409pubmed: 38543774google scholar: lookup
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