1887

Abstract

All herpesviruses have a post-transcriptional regulatory protein that prevents precursor mRNA splicing and leads to the shutting off of host protein synthesis. The ICP27 protein of herpes simplex virus 1 (HSV-1) is the prototype of these proteins. Marek’s disease virus (MDV-1), an alphaherpesvirus that induces lymphoma in birds, also has an ICP27 protein that is produced in lytic MDV-1-infected cells. We characterized this protein. We demonstrated ICP27 production in latently infected MSB-1 cells, but only on MDV-1 reactivation. ICP27 was found predominantly in specific structures within the nucleus. The ICP27 of MDV-1 colocalized and interacted with SR proteins. We demonstrated inhibitory effects of MDV-1 ICP27 on the splicing of both the viral and cellular (telomerase reverse transcriptase) genes. Thus, the ICP27 of MDV-1 plays a similar role to the ICP27 of HSV-1 and may be involved in MDV-1 replication and the development of Marek’s disease.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.028969-0
2011-06-01
2019-12-11
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/6/1273.html?itemId=/content/journal/jgv/10.1099/vir.0.028969-0&mimeType=html&fmt=ahah

References

  1. Akiyama Y., Kato S.. ( 1974;). Two cell lines from lymphomas of Marek’s disease. . Biken J 17:, 105–116.[PubMed]
    [Google Scholar]
  2. Amor S., Remy S., Dambrine G., Le Vern Y., Rasschaert D., Laurent S.. ( 2010;). Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo. . BMC Cancer 10:, 571. [CrossRef][PubMed]
    [Google Scholar]
  3. Debba-Pavard M., Ait-Lounis A., Soubieux D., Rasschaert D., Dambrine G.. ( 2008;). Vaccination against Marek’s disease reduces telomerase activity and viral gene transcription in peripheral blood leukocytes from challenged chickens. . Vaccine 26:, 4904–4912. [CrossRef][PubMed]
    [Google Scholar]
  4. Escudero-Paunetto L., Li L., Hernandez F. P., Sandri-Goldin R. M.. ( 2010;). SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs. . Virology 401:, 155–164. [CrossRef][PubMed]
    [Google Scholar]
  5. Hardwicke M. A., Sandri-Goldin R. M.. ( 1994;). The herpes simplex virus regulatory protein ICP27 contributes to the decrease in cellular mRNA levels during infection. . J Virol 68:, 4797–4810.[PubMed]
    [Google Scholar]
  6. Hardy W. R., Sandri-Goldin R. M.. ( 1994;). Herpes simplex virus inhibits host cell splicing, and regulatory protein ICP27 is required for this effect. . J Virol 68:, 7790–7799.[PubMed]
    [Google Scholar]
  7. Himly M., Foster D. N., Bottoli I., Iacovoni J. S., Vogt P. K.. ( 1998;). The DF-1 chicken fibroblast cell line: transformation induced by diverse oncogenes and cell death resulting from infection by avian leukosis viruses. . Virology 248:, 295–304. [CrossRef][PubMed]
    [Google Scholar]
  8. Laurent S., Vautherot J. F., Le Gall G., Madelaine M. F., Rasschaert D.. ( 1997;). Structural, antigenic and immunogenic relationships between European brown hare syndrome virus and rabbit haemorrhagic disease virus. . J Gen Virol 78:, 2803–2811.[PubMed]
    [Google Scholar]
  9. Laurent A. M., Madjar J. J., Greco A.. ( 1998;). Translational control of viral and host protein synthesis during the course of herpes simplex virus type 1 infection: evidence that initiation of translation is the limiting step. . J Gen Virol 79:, 2765–2775.[PubMed]
    [Google Scholar]
  10. Long J. C., Caceres J. F.. ( 2009;). The SR protein family of splicing factors: master regulators of gene expression. . Biochem J 417:, 15–27. [CrossRef][PubMed]
    [Google Scholar]
  11. Majerciak V., Yamanegi K., Allemand E., Kruhlak M., Krainer A. R., Zheng Z. M.. ( 2008;). Kaposi’s sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing. . J Virol 82:, 2792–2801. [CrossRef][PubMed]
    [Google Scholar]
  12. Malik P., Schirmer E. C.. ( 2006;). The Kaposi’s sarcoma-associated herpesvirus ORF57 protein: a pleurotropic regulator of gene expression. . Biochem Soc Trans 34:, 705–710. [CrossRef][PubMed]
    [Google Scholar]
  13. Mettenleiter T. C., Klupp B. G., Granzow H.. ( 2009;). Herpesvirus assembly: an update. . Virus Res 143:, 222–234. [CrossRef][PubMed]
    [Google Scholar]
  14. Moriuchi H., Moriuchi M., Smith H. A., Cohen J. I.. ( 1994;). Varicella-zoster virus open reading frame 4 protein is functionally distinct from and does not complement its herpes simplex virus type 1 homolog, ICP27. . J Virol 68:, 1987–1992.[PubMed]
    [Google Scholar]
  15. Neugebauer K. M., Stolk J. A., Roth M. B.. ( 1995;). A conserved epitope on a subset of SR proteins defines a larger family of pre-mRNA splicing factors. . J Cell Biol 129:, 899–908. [CrossRef][PubMed]
    [Google Scholar]
  16. Nojima T., Oshiro-Ideue T., Nakanoya H., Kawamura H., Morimoto T., Kawaguchi Y., Kataoka N., Hagiwara M.. ( 2009;). Herpesvirus protein ICP27 switches PML isoform by altering mRNA splicing. . Nucleic Acids Res 37:, 6515–6527. [CrossRef][PubMed]
    [Google Scholar]
  17. Osterrieder N., Kamil J. P., Schumacher D., Tischer B. K., Trapp S.. ( 2006;). Marek’s disease virus: from miasma to model. . Nat Rev Microbiol 4:, 283–294. [CrossRef][PubMed]
    [Google Scholar]
  18. 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]
  19. Parcells M. S., Lin S. F., Dienglewicz R. L., Majerciak V., Robinson D. R., Chen H. C., Wu Z., Dubyak G. R., Brunovskis P. et al. ( 2001;). Marek’s disease virus (MDV) encodes an interleukin-8 homolog (vIL-8): characterization of the vIL-8 protein and a vIL-8 deletion mutant MDV. . J Virol 75:, 5159–5173. [CrossRef][PubMed]
    [Google Scholar]
  20. 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]
  21. 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][PubMed]
    [Google Scholar]
  22. Ruvolo V., Sun L., Howard K., Sung S., Delecluse H. J., Hammerschmidt W., Swaminathan S.. ( 2004;). Functional analysis of Epstein-Barr virus SM protein: identification of amino acids essential for structure, transactivation, splicing inhibition, and virion production. . J Virol 78:, 340–352. [CrossRef][PubMed]
    [Google Scholar]
  23. Sandri-Goldin R. M., Hibbard M. K., Hardwicke M. A.. ( 1995;). The C-terminal repressor region of herpes simplex virus type 1 ICP27 is required for the redistribution of small nuclear ribonucleoprotein particles and splicing factor SC35; however, these alterations are not sufficient to inhibit host cell splicing. . J Virol 69:, 6063–6076.[PubMed]
    [Google Scholar]
  24. Sciabica K. S., Dai Q. J., Sandri-Goldin R. M.. ( 2003;). ICP27 interacts with SRPK1 to mediate HSV splicing inhibition by altering SR protein phosphorylation. . EMBO J 22:, 1608–1619. [CrossRef][PubMed]
    [Google Scholar]
  25. Shkreli M., Dambrine G., Soubieux D., Kut E., Rasschaert D.. ( 2007;). Involvement of the oncoprotein c-Myc in viral telomerase RNA gene regulation during Marek’s disease virus-induced lymphomagenesis. . J Virol 81:, 4848–4857. [CrossRef][PubMed]
    [Google Scholar]
  26. Smith R. W., Malik P., Clements J. B.. ( 2005;). The herpes simplex virus ICP27 protein: a multifunctional post-transcriptional regulator of gene expression. . Biochem Soc Trans 33:, 499–501. [CrossRef][PubMed]
    [Google Scholar]
  27. 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][PubMed]
    [Google Scholar]
  28. Zhi Y., Sandri-Goldin R. M.. ( 1999;). Analysis of the phosphorylation sites of herpes simplex virus type 1 regulatory protein ICP27. . J Virol 73:, 3246–3257.[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.028969-0
Loading
/content/journal/jgv/10.1099/vir.0.028969-0
Loading

Data & Media loading...

Supplements

Primers used in this study. [PDF](47 KB)

PDF

DNA fragment analysis corresponding to PCR amplification products of intron 1 of vIL8 in MSB1 cells (a) and intron 14 of chTERT in DF1 (b). PCRs were performed in Ready Master Mix 1.1X (Abgene) with specific tetrachlorofluorescein phosphoramidite (TET)-labelled forward primers and unlabelled reverse primers specific (see Supplementary Table S1). PCR products were analysed with an automated ABI Prism 310 fragment analyser (Perkin Elmer Life Sciences). On the electrophoregram, a Gene scan-500 tetraethylrhodamine (TAMRA) size standard (Applied Biosystems) corresponded to the white open peaks and PCR products to the grey peaks. Sizes of corresponding products are indicated. The ratio of intron retention was determined as a percentage of the peak area for spliced versus non-spliced transcripts.

IMAGE

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