1887

Abstract

Equine herpesvirus type 1 (EHV-1) replicates in the epithelial cells of the upper respiratory tract and disseminates through the body via a cell-associated viraemia in monocytic cells, despite the presence of neutralizing antibodies. However, the mechanism by which EHV-1 hijacks immune cells and uses them as ‘Trojan horses’ in order to disseminate inside its host is still unclear. Here, we hypothesize that EHV-1 delays its replication in monocytic cells in order to avoid recognition by the immune system. We compared replication kinetics of EHV-1 in RK-13, a cell line fully susceptible to EHV-1 infection, and primary horse cells from the myeloid lineage (CD172a). We found that EHV-1 replication was restricted to 4 % of CD172a cells compared with 100 % in RK-13 cells. In susceptible CD172a cells, the expression of immediate-early (IEP) and early (EICP22) proteins was delayed in the cell nuclei by 2–3 h post-infection (p.i.) compared with RK-13, and the formation of replicative compartments by 15 h p.i. Virus production in CD172a cells was significantly lower (from 10 to 10 TCID per 10 inoculated cells) than in RK-13 (from 10 to 10 TCID per 10 inoculated cells). Less than 0.02 % of inoculated CD172a cells produced and transmitted infectious virus to neighbouring cells. Pre-treatment of CD172a cells with inhibitors of histone deacetylase activity increased and accelerated viral protein expression at very early times of infection and induced productive infection in CD172a cells. Our results demonstrated that the restriction and delay of EHV-1 replication in CD172a cells are part of an immune evasive strategy and involve silencing of EHV-1 gene expression associated with histone deacetylases.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.067363-0
2015-01-01
2019-12-08
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/1/118.html?itemId=/content/journal/jgv/10.1099/vir.0.067363-0&mimeType=html&fmt=ahah

References

  1. Alcami A., Koszinowski U. H.. ( 2000;). Viral mechanisms of immune evasion. . Immunol Today 21:, 447–455. [CrossRef][PubMed]
    [Google Scholar]
  2. Allen G. P., Bryans J. T.. ( 1986;). Molecular epizootiology, pathogenesis, and prophylaxis of equine herpesvirus-1 infections. . Prog Vet Microbiol Immunol 2:, 78–144.[PubMed]
    [Google Scholar]
  3. Baghi H. B., Laval K., Favoreel H. W., Nauwynck H. J.. ( 2014;). Isolation and characterization of equine nasal mucosal CD172a+ cells. . Vet Immunol Immunopathol 157:, 155–163. [CrossRef][PubMed]
    [Google Scholar]
  4. Bergamaschi A., Pancino G.. ( 2010;). Host hindrance to HIV-1 replication in monocytes and macrophages. . Retrovirology 7:, 31. [CrossRef][PubMed]
    [Google Scholar]
  5. Boomker J. M., de Leij L. F. M. H. L., The T. H., Harmsen M. C.. ( 2005;). Viral chemokine-modulatory proteins: tools and targets. . Cytokine Growth Factor Rev 16:, 91–103. [CrossRef][PubMed]
    [Google Scholar]
  6. Chang L., Godinez W. J., Kim I. H., Tektonidis M., de Lanerolle P., Eils R., Rohr K., Knipe D. M.. ( 2011;). Herpesviral replication compartments move and coalesce at nuclear speckles to enhance export of viral late mRNA. . Proc Natl Acad Sci U S A 108:, E136–E144. [CrossRef][PubMed]
    [Google Scholar]
  7. Cody J. J., Markert J. M., Hurst D. R.. ( 2014;). Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells. . PLoS ONE 9:, e92919. [CrossRef][PubMed]
    [Google Scholar]
  8. Digel M., Sampaio K. L., Jahn G., Sinzger C.. ( 2006;). Evidence for direct transfer of cytoplasmic material from infected to uninfected cells during cell-associated spread of human cytomegalovirus. . J Clin Virol 37:, 10–20. [CrossRef][PubMed]
    [Google Scholar]
  9. Dunowska M.. ( 2014;). A review of equid herpesvirus 1 for the veterinary practitioner. Part B: pathogenesis and epidemiology. . N Z Vet J 62:, 179–188. [CrossRef][PubMed]
    [Google Scholar]
  10. Edington N., Smyth B., Griffiths L.. ( 1991;). 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. [CrossRef][PubMed]
    [Google Scholar]
  11. Efstathiou S., Preston C. M.. ( 2005;). Towards an understanding of the molecular basis of herpes simplex virus latency. . Virus Res 111:, 108–119. [CrossRef][PubMed]
    [Google Scholar]
  12. Everett R. D., Parsy M. L., Orr A.. ( 2009;). Analysis of the functions of herpes simplex virus type 1 regulatory protein ICP0 that are critical for lytic infection and derepression of quiescent viral genomes. . J Virol 83:, 4963–4977. [CrossRef][PubMed]
    [Google Scholar]
  13. Favoreel H. W., Van de Walle G. R., Nauwynck H. J., Pensaert M. B.. ( 2003;). Virus complement evasion strategies. . J Gen Virol 84:, 1–15. [CrossRef][PubMed]
    [Google Scholar]
  14. Feng W. H., Kenney S. C.. ( 2006;). Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression. . Cancer Res 66:, 8762–8769. [CrossRef][PubMed]
    [Google Scholar]
  15. Gerna G., Percivalle E., Baldanti F., Sozzani S., Lanzarini P., Genini E., Lilleri D., Revello M. G.. ( 2000;). Human cytomegalovirus replicates abortively in polymorphonuclear leukocytes after transfer from infected endothelial cells via transient microfusion events. . J Virol 74:, 5629–5638. [CrossRef][PubMed]
    [Google Scholar]
  16. Goehring L. S., van Winden S. C., van Maanen C., Sloet van Oldruitenborgh-Oosterbaan M. M.. ( 2006;). Equine herpesvirus type 1-associated myeloencephalopathy in The Netherlands: a four-year retrospective study (1999–2003). . J Vet Intern Med 20:, 601–607.[PubMed]
    [Google Scholar]
  17. Göttlicher M., Minucci S., Zhu P., Krämer O. H., Schimpf A., Giavara S., Sleeman J. P., Lo Coco F., Nervi C.. & other authors ( 2001;). Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. . EMBO J 20:, 6969–6978. [CrossRef][PubMed]
    [Google Scholar]
  18. Gryspeerdt A. C., Vandekerckhove A. P., Garré B., Barbé F., Van de Walle G. R., Nauwynck H. J.. ( 2010;). Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses. . Vet Microbiol 142:, 242–253. [CrossRef][PubMed]
    [Google Scholar]
  19. Gryspeerdt A. C., Vandekerckhove A. P., Baghi H. B., Van de Walle G. R., Nauwynck H. J.. ( 2012;). 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. [CrossRef][PubMed]
    [Google Scholar]
  20. Jang H. K., Albrecht R. A., Buczynski K. A., Kim S. K., Derbigny W. A., O’Callaghan D. J.. ( 2001;). Mapping the sequences that mediate interaction of the equine herpesvirus 1 immediate-early protein and human TFIIB. . J Virol 75:, 10219–10230. [CrossRef][PubMed]
    [Google Scholar]
  21. Knipe D. M., Senechek D., Rice S. A., Smith J. L.. ( 1987;). Stages in the nuclear association of the herpes simplex virus transcriptional activator protein ICP4. . J Virol 61:, 276–284.[PubMed]
    [Google Scholar]
  22. Kydd J. H., Townsend H. G., Hannant D.. ( 2006;). The equine immune response to equine herpesvirus-1: the virus and its vaccines. . Vet Immunol Immunopathol 111:, 15–30. [CrossRef][PubMed]
    [Google Scholar]
  23. Meier J. L.. ( 2001;). Reactivation of the human cytomegalovirus major immediate-early regulatory region and viral replication in embryonal NTera2 cells: role of trichostatin A, retinoic acid, and deletion of the 21-base-pair repeats and modulator. . J Virol 75:, 1581–1593. [CrossRef][PubMed]
    [Google Scholar]
  24. Murphy J. C., Fischle W., Verdin E., Sinclair J. H.. ( 2002;). Control of cytomegalovirus lytic gene expression by histone acetylation. . EMBO J 21:, 1112–1120. [CrossRef][PubMed]
    [Google Scholar]
  25. Nauwynck H. J., Pensaert M. B.. ( 1994;). Virus production and viral antigen expression in porcine blood monocytes inoculated with pseudorabies virus. . Arch Virol 137:, 69–79. [CrossRef][PubMed]
    [Google Scholar]
  26. Nikolic D. S., Lehmann M., Felts R., Garcia E., Blanchet F. P., Subramaniam S., Piguet V.. ( 2011;). HIV-1 activates Cdc42 and induces membrane extensions in immature dendritic cells to facilitate cell-to-cell virus propagation. . Blood 118:, 4841–4852. [CrossRef][PubMed]
    [Google Scholar]
  27. O’Neill T., Kydd J. H., Allen G. P., Wattrang E., Mumford J. A., Hannant D.. ( 1999;). Determination of equid herpesvirus 1-specific, CD8+, cytotoxic T lymphocyte precursor frequencies in ponies. . Vet Immunol Immunopathol 70:, 43–54. [CrossRef][PubMed]
    [Google Scholar]
  28. Patel J. R., Heldens J.. ( 2005;). Equine herpesviruses 1 (EHV-1) and 4 (EHV-4) – epidemiology, disease and immunoprophylaxis: a brief review. . Vet J 170:, 14–23. [CrossRef][PubMed]
    [Google Scholar]
  29. Quinlan M. P., Chen L. B., Knipe D. M.. ( 1984;). The intranuclear location of a herpes simplex virus DNA-binding protein is determined by the status of viral DNA replication. . Cell 36:, 857–868. [CrossRef][PubMed]
    [Google Scholar]
  30. Reed L. J., Muench H.. ( 1938;). A simple method for estimating fifty percent endpoints. . Am J Hyg 27:, 493–497.
    [Google Scholar]
  31. Rice G. P., Schrier R. D., Oldstone M. B.. ( 1984;). Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. . Proc Natl Acad Sci U S A 81:, 6134–6138. [CrossRef][PubMed]
    [Google Scholar]
  32. Slater J.. ( 2007;). Equine herpesviruses. . In Equine Infectious Diseases, pp. 134–153. Edited by Sellon D. C., Long M. T... St Louis:: Saunders Elsevier;. [CrossRef]
    [Google Scholar]
  33. Smith R. H., Zhao Y., O’Callaghan D. J.. ( 1994;). The equine herpesvirus type 1 immediate-early gene product contains an acidic transcriptional activation domain. . Virology 202:, 760–770. [CrossRef][PubMed]
    [Google Scholar]
  34. Smith K. C., Mumford J. A., Lakhani K.. ( 1996;). A comparison of equid herpesvirus-1 (EHV-1) vascular lesions in the early versus late pregnant equine uterus. . J Comp Pathol 114:, 231–247. [CrossRef][PubMed]
    [Google Scholar]
  35. Smith M. S., Bentz G. L., Alexander J. S., Yurochko A. D.. ( 2004;). Human cytomegalovirus induces monocyte differentiation and migration as a strategy for dissemination and persistence. . J Virol 78:, 4444–4453. [CrossRef][PubMed]
    [Google Scholar]
  36. Stierstorfer B., Eichhorn W., Schmahl W., Brandmüller C., Kaaden O. R., Neubauer A.. ( 2002;). Equine herpesvirus type 1 (EHV-1) myeloencephalopathy: a case report. . J Vet Med B Infect Dis Vet Public Health 49:, 37–41. [CrossRef][PubMed]
    [Google Scholar]
  37. Taylor T. J., McNamee E. E., Day C., Knipe D. M.. ( 2003;). Herpes simplex virus replication compartments can form by coalescence of smaller compartments. . Virology 309:, 232–247. [CrossRef][PubMed]
    [Google Scholar]
  38. Thormar H.. ( 2005;). Maedi-visna virus and its relationship to human immunodeficiency virus. . AIDS Rev 7:, 233–245.[PubMed]
    [Google Scholar]
  39. van der Meulen K. M., Nauwynck H. J., Buddaert W., Pensaert M. B.. ( 2000;). Replication of equine herpesvirus type 1 in freshly isolated equine peripheral blood mononuclear cells and changes in susceptibility following mitogen stimulation. . J Gen Virol 81:, 21–25.[PubMed]
    [Google Scholar]
  40. van der Meulen K., Caij B., Pensaert M., Nauwynck H.. ( 2006;). Absence of viral envelope proteins in equine herpesvirus 1-infected blood mononuclear cells during cell-associated viremia. . Vet Microbiol 113:, 265–273. [CrossRef][PubMed]
    [Google Scholar]
  41. Vandekerckhove A. P., Glorieux S., Gryspeerdt A. C., Steukers L., Duchateau L., Osterrieder N., Van de Walle G. R., Nauwynck H. J.. ( 2010;). Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants. . J Gen Virol 91:, 2019–2028. [CrossRef][PubMed]
    [Google Scholar]
  42. Vandekerckhove A. P., Glorieux S., Gryspeerdt A. C., Steukers L., Van Doorsselaere J., Osterrieder N., Van de Walle G. R., Nauwynck H. J.. ( 2011;). 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 152:, 21–28. [CrossRef][PubMed]
    [Google Scholar]
  43. Vossen M. T., Westerhout E. M., Söderberg-Nauclér C., Wiertz E. J.. ( 2002;). Viral immune evasion: a masterpiece of evolution. . Immunogenetics 54:, 527–542. [CrossRef][PubMed]
    [Google Scholar]
  44. Wright E., Bain M., Teague L., Murphy J., Sinclair J.. ( 2005;). Ets-2 repressor factor recruits histone deacetylase to silence human cytomegalovirus immediate-early gene expression in non-permissive cells. . J Gen Virol 86:, 535–544. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.067363-0
Loading
/content/journal/jgv/10.1099/vir.0.067363-0
Loading

Data & Media loading...

Supplements

Supplementary Data



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error