1887

Abstract

Marek’s disease virus (MDV) is a herpesvirus that induces lymphoma and a variety of non-neoplastic syndromes in chickens. Furthermore, very virulent plus (vv+) MDVs induce a form of immunosuppression (late-MDV-IS) that might involve both neoplastic and non-neoplastic mechanisms. The objective of this study was to evaluate whether the attenuation of MDV-induced tumours and late-MDV-IS occurs simultaneously or can be dissociated. The immunosuppressive ability of three viruses derived from vv+ MDV strain 686 (wild-type 686, the somewhat attenuated molecular clone 686-BAC, and the nononcogenic molecular clone lacking the two copies of the oncogene meq 686-BACΔMEQ) was evaluated. Late-MDV-IS was evaluated indirectly by assessing the negative effect of MDV strains on the protection conferred by infectious laryngotracheitis (ILT) vaccines. Our results showed that the ability to induce late-MDV-IS was attenuated before the ability to induce tumours. Strain 686 induced both tumours and late-MDV-IS, 686-BAC induced tumours but did not induce late-MDV-IS and 686-BACΔMEQ did not induce either tumours or late-MDV-IS. Further comparison of strains 686 and 686-BAC revealed that strain 686 reduced the humoral immune responses to ILTV (1132 vs 2167) more severely, showed higher levels of meq transcripts (2.1E+09 vs 4.98E+8) and higher expression of MDV microRNAs (mdv1-miR-M4-5p and mdv1-miR-M2-3p) in the spleen, and further reduced the percentage of CD45-MHC-Isplenocytes (13 vs32 %) compared to molecular clone 686-BAC. This study suggests that the immunosuppressive ability of MDV might follow a continuous spectrum and only the most virulent MDVs can overcome a certain threshold level and induce clinical MDV-IS in the ILT model.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001076
2018-07-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/7/927.html?itemId=/content/journal/jgv/10.1099/jgv.0.001076&mimeType=html&fmt=ahah

References

  1. Calnek BW. Pathogenesis of Marek's disease virus infection. In Hirai K. (editor) Current Topics in Microbiology and Immunology Berlin: Springer-Verlag; 2001 pp. 25–56
    [Google Scholar]
  2. Schat KA. Marek's disease immunosuppression. In Davison F, Venugopal N. (editors) Marek's Disease an Evolving Problem Compton: Elsevier; 2004 pp. 142–155 [Crossref]
    [Google Scholar]
  3. Churchill AE, Baxendale W. Virus effect of lyophilized turkey herpesvirus – Marek's vaccines in chicks with maternal antibodies against turkey herpesvirus. Wien TierarztlMonatsschr 1973; 60:248–254
    [Google Scholar]
  4. Payne LN, Rennie M. Pathogenesis of Marek's disease in chicks with and without maternal antibody. J Natl Cancer Inst 1973; 51:1559–1573 [View Article][PubMed]
    [Google Scholar]
  5. Quere P. Suppression mediated in vitro by Marek's disease virus-transformed T-lymphoblastoid cell lines: effect on lymphoproliferation. Vet Immunol Immunopathol 1992; 32:149–164 [View Article][PubMed]
    [Google Scholar]
  6. Ohashi K, Mikami T, Kodama H, Izawa H. Suppression of NK activity of spleen cells by chicken fetal antigen present on Marek's disease lymphoblastoid cell line cells. Int J Cancer 1987; 40:378–382 [View Article][PubMed]
    [Google Scholar]
  7. Kaiser P, Underwood G, Davison F. Differential cytokine responses following Marek's disease virus infection of chickens differing in resistance to Marek's disease. J Virol 2003; 77:762–768 [View Article][PubMed]
    [Google Scholar]
  8. Hunt HD, Lupiani B, Miller MM, Gimeno I, Lee LF et al. Marek's disease virus down-regulates surface expression of MHC (B Complex) Class I (BF) glycoproteins during active but not latent infection of chicken cells. Virology 2001; 282:198–205 [View Article][PubMed]
    [Google Scholar]
  9. Gimeno IM, Witter RL, Hunt HD, Lee LF, Reddy SM et al. Marek's disease virus infection in the brain: virus replication, cellular infiltration, and major histocompatibility complex antigen expression. Vet Pathol 2001; 38:491–503 [View Article][PubMed]
    [Google Scholar]
  10. Morimura T, Ohashi K, Kon Y, Hattori M, Sugimoto C et al. Apoptosis and CD8-down-regulation in the thymus of chickens infected with Marek's disease virus - Brief report. ArchVirol 1996; 141:2243–2249
    [Google Scholar]
  11. Morgan RW, Stevenson N, Bernberg E, Isaacs G, Anderson A et al. (editors) Expression Of marek’s Disease Virus Microrna Mdv1-Mir-M4 Increases Susceptibility of Young Chicks To salmonella Enteriditis 2013 AVMA/AAAP Annual Convention Chicago: AAAP; 2013
    [Google Scholar]
  12. Faiz NM, Cortes AL, Guy JS, Fletcher OJ, West M et al. Early infection with Marek's disease virus can jeopardize protection conferred by laryngotracheitis vaccines: a method to study MDV-induced immunosuppression. Avian Pathol 2016; 45:606–615 [View Article][PubMed]
    [Google Scholar]
  13. Faiz NM, Cortes AL, Guy JS, Fogle JE, Gimeno IM. Efficacy of various Marek's disease vaccines protocols for prevention of Marek's disease virus-induced immunosuppression. Vaccine 2016; 34:4180–4187 [View Article][PubMed]
    [Google Scholar]
  14. Gimeno IM, Witter RL, Hunt HD, Reddy SM, Neumann U. Differential attenuation of the induction by Marek's disease virus of transient paralysis and persistent neurological disease: a model for pathogenesis studies. Avian Pathol 2001; 30:397–409 [View Article][PubMed]
    [Google Scholar]
  15. Matsuyama-Kato A, Murata S, Isezaki M, Kano R, Takasaki S et al. Molecular characterization of immunoinhibitory factors PD-1/PD-L1 in chickens infected with Marek's disease virus. Virol J 2012; 9:94 [View Article][PubMed]
    [Google Scholar]
  16. Jarosinski KW, Hunt HD, Osterrieder N. Down-regulation of MHC class I by the Marek's disease virus (MDV) UL49.5 gene product mildly affects virulence in a haplotype-specific fashion. Virology 2010; 405:457–463 [View Article][PubMed]
    [Google Scholar]
  17. Witter RL. Increased virulence of Marek's disease virus field isolates. Avian Dis 1997; 41:149–163 [View Article][PubMed]
    [Google Scholar]
  18. Witter RL, Calnek BW, Buscaglia C, Gimeno IM, Schat KA. Classification of Marek's disease viruses according to pathotype: philosophy and methodology. Avian Pathol 2005; 34:75–90 [View Article][PubMed]
    [Google Scholar]
  19. Faiz NM, Cortes AL, Guy JS, Fletcher OJ, Cimino T et al. Evaluation of factors influencing the development of late Marek’s disease virus-induced immunosuppression: virus pathotype and host sex. Avian Pathology 2017; 46:376–385 [View Article]
    [Google Scholar]
  20. Reddy SM, Sun A, Khan OA, Lee LF, Lupiani B. Cloning of a very virulent plus, 686 strain of Marek's disease virus as a bacterial artificial chromosome. Avian Dis 2013; 57:469–473 [View Article][PubMed]
    [Google Scholar]
  21. Dunn JR, Reddy SM, Niikura M, Nair V, Fulton JE et al. Evaluation and identification of Marek's disease virus BAC clones as standardized reagents for research. Avian Dis 2017; 61:107–114 [View Article][PubMed]
    [Google Scholar]
  22. Lupiani B, Lee LF, Cui X, Gimeno I, Anderson A et al. Marek's disease virus-encoded Meq gene is involved in transformation of lymphocytes but is dispensable for replication. Proc Natl Acad Sci USA 2004; 101:11815–11820 [View Article][PubMed]
    [Google Scholar]
  23. Parcells MS, Arumugaswami V, Prigge JT, Pandya K, Dienglewicz RL. Marek's disease virus reactivation from latency: changes in gene expression at the origin of replication. Poult Sci 2003; 82:893–898 [View Article][PubMed]
    [Google Scholar]
  24. Venugopal K, Payne LN. Molecular pathogenesis of Marek's disease-recent developments. Avian Pathol 1995; 24:597–609 [View Article][PubMed]
    [Google Scholar]
  25. Yu C, Liu Q, Qin A, Hu X, Xu W et al. Expression kinetics of chicken β2-microglobulin and Class I MHC in vitro and in vivo during Marek's disease viral infections. Vet Res Commun 2013; 37:277–283 [View Article][PubMed]
    [Google Scholar]
  26. Fahey KJ, York JJ. The role of mucosal antibody in immunity to infectious laryngotracheitis virus in chickens. J Gen Virol 1990; 71:2401–2405 [View Article][PubMed]
    [Google Scholar]
  27. Islam AF, Wong CW, Walkden-Brown SW, Colditz IG, Arzey KE et al. Immunosuppressive effects of Marek's disease virus (MDV) and herpesvirus of turkeys (HVT) in broiler chickens and the protective effect of HVT vaccination against MDV challenge. Avian Pathol 2002; 31:449–461 [View Article][PubMed]
    [Google Scholar]
  28. Reddy SK, Suresh M, Karaca K, Sharma JM, McMillen J et al. Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens. Vaccine 1996; 14:1695–1702 [View Article][PubMed]
    [Google Scholar]
  29. Rivas AL, Fabricant J. Indications of immunodepression in chickens infected with various strains of Marek's disease virus. Avian Dis 1988; 32:1–8 [View Article][PubMed]
    [Google Scholar]
  30. Li Y, Sun A, Su S, Zhao P, Cui Z et al. Deletion of the Meq gene significantly decreases immunosuppression in chickens caused by pathogenic Marek's disease virus. Virol J 2011; 8:2–8 [View Article][PubMed]
    [Google Scholar]
  31. Marty EW, Winans RE. Immunizing characteristics of a tissue-culture-origin modified live-virus ocular vaccine for infectious laryngotracheitis. Avian Dis 1971; 15:277–283 [View Article][PubMed]
    [Google Scholar]
  32. Gimeno IM, Witter RL, Fadly AM, Silva RF. Novel criteria for the diagnosis of Marek's disease virus-induced lymphomas. Avian Pathol 2005; 34:332–340 [View Article][PubMed]
    [Google Scholar]
  33. Gimeno IM, Cortes AL, Silva RF. Load of challenge Marek's disease virus DNA in blood as a criterion for early diagnosis of Marek's disease tumors. Avian Dis 2008; 52:203–208 [View Article][PubMed]
    [Google Scholar]
  34. Gimeno IM, Cortes AL, Montiel ER, Lemiere S, Pandiri AK. Effect of diluting Marek's disease vaccines on the outcomes of Marek's disease virus infection when challenged with highly virulent Marek's disease viruses. Avian Dis 2011; 55:263–272 [View Article][PubMed]
    [Google Scholar]
  35. Gimeno IM, Dunn JR, Cortes AL, El-Gohary A-G, Silva RF. Detection and differentiation of CVI988 (Rispens vaccine) from other serotype 1 Marek's disease viruses. Avian Dis 2014; 58:232–243 [View Article][PubMed]
    [Google Scholar]
  36. Cortes AL, Montiel ER, Lemiere S, Gimeno IM. Comparison of blood and feather pulp samples for the diagnosis of Marek's disease and for monitoring Marek's disease vaccination by real time-PCR. Avian Dis 2011; 55:302–310 [View Article][PubMed]
    [Google Scholar]
  37. Gimeno IM, Cortes AL. Chronological study of cytokine transcription in the spleen and lung of chickens after vaccination with serotype 1 Marek's disease vaccines. Vaccine 2011; 29:1583–1594 [View Article][PubMed]
    [Google Scholar]
  38. Swaggerty CL, Pevzner IY, Kaiser P, Kogut MH. Profiling pro-inflammatory cytokine and chemokine mRNA expression levels as a novel method for selection of increased innate immune responsiveness. Vet Immunol Immunopathol 2008; 126:35–42 [View Article][PubMed]
    [Google Scholar]
  39. Burnside J, Bernberg E, Anderson A, Lu C, Meyers BC et al. Marek's disease virus encodes MicroRNAs that map to meq and the latency-associated transcript. J Virol 2006; 80:8778–8786 [View Article][PubMed]
    [Google Scholar]
  40. Paramithiotis E, Tkalec L, Ratcliffe MJ. High levels of CD45 are coordinately expressed with CD4 and CD8 on avian thymocytes. J Immunol 1991; 147:3710–3717[PubMed]
    [Google Scholar]
  41. Salomonsen J, Skjødt K, Crone M, Simonsen M. The chicken erythrocyte-specific MHC antigen. Characterization and purification of the B-G antigen by monoclonal antibodies. Immunogenetics 1987; 25:373–382 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001076
Loading
/content/journal/jgv/10.1099/jgv.0.001076
Loading

Data & Media loading...

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