1887

Abstract

Herpesvirus gene expression is temporally regulated, with immediate early (IE), early (E) and late (L) genes. ICP27, which is involved in post-transcriptional regulation, is the only IE gene product conserved in all herpesviruses. We show here that the ICP27 transcript of the oncogenic Marek’s disease virus shares the same polyadenylation signal as the bicistronic glycoprotein K–ICP27 transcript and is regulated by alternative promoter usage, with transcription from its own promoter (pICP27) or that of gK (pgK). The pgK can generate a spliced ICP27 transcript yielding an N-terminal-deleted ICP27 isoform (ICP27ΔN) that, like ICP27, co-localizes with the SR protein in infected cells, but with a diffuse nuclear distribution. The pICP27 includes functional responsive elements (REs) for SP1, AP1 and CREB, is essentially active during the lytic phase and leads to exclusive expression of the native form of ICP27. The alternative promoter, pgK, including active REs for GATA, P53 and CREB, preferentially generates the gK transcript during the lytic phase and the spliced ICP27 transcript (ICP27ΔN) during the latent phase. An analysis of the DNA methylation marks of each promoter showed that pgK was systematically demethylated, whereas pICP27 was methylated during latency and demethylated during the lytic stage. Thus, MDV gene expression is dependent on alternative promoters, the usage of which is regulated by DNA methylation, which differs between viral stages.

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2016-09-01
2019-12-08
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References

  1. Akiyama Y., Kato S., Iwa N..( 1973;). Continuous cell culture from lymphoma of Marek's disease. . Biken J 16: 177–179.
    [Google Scholar]
  2. Amor S., Strassheim S., Dambrine G., Remy S., Rasschaert D., Laurent S..( 2011;). ICP27 protein of Marek's disease virus interacts with SR proteins and inhibits the splicing of cellular telomerase chTERT and viral vIL8 transcripts. . J Gen Virol 92: 1273–1278. [CrossRef]
    [Google Scholar]
  3. Baba T. W., Giroir B. P., Humphries E. H..( 1985;). Cell lines derived from avian lymphomas exhibit two distinct phenotypes. . Virology 144: 139–151. [CrossRef]
    [Google Scholar]
  4. Brown A. C., Nair V., Allday M. J..( 2012;). Epigenetic regulation of the latency-associated region of Marek's disease virus in tumor-derived T-cell lines and primary lymphoma. . J Virol 86: 1683–1695. [CrossRef] [PubMed]
    [Google Scholar]
  5. Byun H., Gwack Y., Hwang S., Choe J..( 2002;). Kaposi's sarcoma-associated herpesvirus open reading frame (ORF) 50 transactivates K8 and ORF57 promoters via heterogeneous response elements. . Mol Cells 14: 185–191.[PubMed]
    [Google Scholar]
  6. Coupeau D., Dambrine G., Rasschaert D..( 2012;). Kinetic expression analysis of the cluster mdv1-mir-M9-M4, genes meq and vIL-8 differs between the lytic and latent phases of Marek's disease virus infection. . J Gen Virol 93: 1519–1529. [CrossRef]
    [Google Scholar]
  7. Dorange F., Tischer B. K., Vautherot J. F., Osterrieder N..( 2002;). Characterization of Marek's disease virus serotype 1 (MDV-1) deletion mutants that lack UL46 to UL49 genes: MDV-1 UL49, encoding VP22, is indispensable for virus growth. . J Virol 76: 1959–1970. [CrossRef] [PubMed]
    [Google Scholar]
  8. Dorange F., El Mehdaoui S., Pichon C., Coursaget P., Vautherot J. F..( 2000;). Marek's disease virus (MDV) homologues of herpes simplex virus type 1 UL49 (VP22) and UL48 (VP16) genes: high-level expression and characterization of MDV-1 VP22 and VP16. . J Gen Virol 81: 2219–2230. [CrossRef] [PubMed]
    [Google Scholar]
  9. Jackson B. R., Noerenberg M., Whitehouse A..( 2012;). The Kaposi’s sarcoma-associated herpesvirus ORF57 protein and its multiple roles in mRNA biogenesis. . Front Microbiol 3: 59. [CrossRef] [PubMed]
    [Google Scholar]
  10. Johnson D. C., Baines J. D..( 2011;). Herpesviruses remodel host membranes for virus egress. . Nat Rev Microbiol 9: 382–394. [CrossRef] [PubMed]
    [Google Scholar]
  11. Jones D., Lee L., Liu J. L., Kung H. J., Tillotson J. K..( 1992;). Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymphoblastoid tumors. . Proc Natl Acad Sci U S A 89: 4042–4046. [CrossRef] [PubMed]
    [Google Scholar]
  12. Juillard F., Bazot Q., Mure F., Tafforeau L., Macri C., Rabourdin-Combe C., Lotteau V., Manet E., Gruffat H..( 2012;). Epstein-Barr virus protein EB2 stimulates cytoplasmic mRNA accumulation by counteracting the deleterious effects of SRp20 on viral mRNAs. . Nucleic Acids Res 40: 6834–6849. [CrossRef]
    [Google Scholar]
  13. Kato K., Izumiya Y., Tohya Y., Takahashi E., Hirai K., Kawaguchi Y..( 2002;). Identification and characterization of Marek's disease virus serotype 1 (MDV1) ICP22 gene product: MDV1 ICP22 transactivates the MDV1 ICP27 promoter synergistically with MDV1 ICP4. . Vet Microbiol 85: 305–313. [CrossRef] [PubMed]
    [Google Scholar]
  14. Kaufer B. B., Jarosinski K. W., Osterrieder N..( 2011;). Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation. . J Exp Med 208: 605–615. [CrossRef] [PubMed]
    [Google Scholar]
  15. Knipe D. M., Lieberman P. M., Jung J. U., McBride A. A., Morris K. V., Ott M., Margolis D., Nieto A., Nevels M. et al.( 2013;). Snapshots: chromatin control of viral infection. . Virology 435: 141–156. [CrossRef]
    [Google Scholar]
  16. Levy A. M., Izumiya Y., Brunovskis P., Xia L., Parcells M. S., Reddy S. M., Lee L., Chen H. W., Kung H. J..( 2003;). Characterization of the chromosomal binding sites and dimerization partners of the viral oncoprotein Meq in Marek's disease virus-transformed T cells. . J Virol 77: 12841–12851. [CrossRef] [PubMed]
    [Google Scholar]
  17. Nair V..( 2013;). Latency and tumorigenesis in Marek's disease. . Avian Dis 57: 360–365. [CrossRef] [PubMed]
    [Google Scholar]
  18. Neubauer A., Osterrieder N..( 2004;). Equine herpesvirus type 1 (EHV-1) glycoprotein K is required for efficient cell-to-cell spread and virus egress. . Virology 329: 18–32. [CrossRef]
    [Google Scholar]
  19. Osterrieder K., Vautherot J. F..( 2004;). The genome content of Marek's disease-like viruses. . In Marek's Disease: An Evolving Problem , pp. 17–31. Edited by Davison F., Nair V.. Oxford:: Elsevier Academic Press;.[Crossref]
    [Google Scholar]
  20. Ote I., Piette J., Sadzot-Delvaux C..( 2010;). The Varicella-zoster virus IE4 protein: a conserved member of the herpesviral mRNA export factors family and a potential alternative target in antiherpetic therapies. . Biochem Pharmacol 80: 1973–1980. [CrossRef] [PubMed]
    [Google Scholar]
  21. Petherbridge L., Brown A. C., Baigent S. J., Howes K., Sacco M. A., Osterrieder N., Nair V. K..( 2004;). Oncogenicity of virulent Marek's disease virus cloned as bacterial artificial chromosomes. . J Virol 78: 13376–13380. [CrossRef] [PubMed]
    [Google Scholar]
  22. Rahaus M., Wolff M. H..( 2003;). Reciprocal effects of Varicella-zoster virus (VZV) and AP1: activation of jun, fos and ATF-2 after VZV infection and their importance for the regulation of viral genes. . Virus Res 92: 9–21. [CrossRef] [PubMed]
    [Google Scholar]
  23. Ren D., Lee L. F., Coussens P. M..( 1994;). Identification and characterization of Marek's disease virus genes homologous to ICP27 and glycoprotein K of herpes simplex virus-1. . Virology 204: 242–250. [CrossRef]
    [Google Scholar]
  24. Sandri-Goldin R. M..( 2011;). The many roles of the highly interactive HSV protein ICP27, a key regulator of infection. . Future Microbiol 6: 1261–1277. [CrossRef] [PubMed]
    [Google Scholar]
  25. Sandri-Goldin Rozanne, M..( 2008;). The many roles of the regulatory protein ICP27 during herpes simplex virus infection. . Front Biosci 13: 5241–5256. [CrossRef] [PubMed]
    [Google Scholar]
  26. Schat K. A., Nair V..( 2008;). Marek's Disease. . In Diseases of Poultry , pp. 452–514. Edited by Saif Y. M.. Oxford:: Blackwell Publishing;.
    [Google Scholar]
  27. Spatz S. J., Zhao Y., Petherbridge L., Smith L. P., Baigent S. J., Nair V..( 2007;). Comparative sequence analysis of a highly oncogenic but horizontal spread-defective clone of Marek's disease virus. . Virus Genes 35: 753–766. [CrossRef] [PubMed]
    [Google Scholar]
  28. Stik G., Laurent S., Coupeau D., Coutaud B., Dambrine G., Rasschaert D., Muylkens B..( 2010;). A p53-dependent promoter associated with polymorphic tandem repeats controls the expression of a viral transcript encoding clustered microRNAs. . RNA 16: 2263–2276. [CrossRef]
    [Google Scholar]
  29. Strassheim S., Stik G., Rasschaert D., Laurent S..( 2012;). mdv1-miR-M7-5p, located in the newly identified first intron of the latency-associated transcript of Marek's disease virus, targets the immediate-early genes ICP4 and ICP27. . J Gen Virol 93: 1731–1742. [CrossRef] [PubMed]
    [Google Scholar]
  30. Vinson C., Myakishev M., Acharya A., Mir A. A., Moll J. R., Bonovich M..( 2002;). Classification of human B-ZIP proteins based on dimerization properties. . Mol Cell Biol 22: 6321–6335. [CrossRef] [PubMed]
    [Google Scholar]
  31. Weir J. P..( 2001;). Regulation of herpes simplex virus gene expression. . Gene 271: 117–130. [CrossRef] [PubMed]
    [Google Scholar]
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