Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 May 1;89(9):4042–4046. doi: 10.1073/pnas.89.9.4042

Marek disease virus encodes a basic-leucine zipper gene resembling the fos/jun oncogenes that is highly expressed in lymphoblastoid tumors.

D Jones 1, L Lee 1, J L Liu 1, H J Kung 1, J K Tillotson 1
PMCID: PMC525628  PMID: 1315048

Abstract

Marek disease virus (MDV) is a herpesvirus of chickens that induces T lymphomas within 3 weeks of infection. The short latency and polyclonal nature of MDV-induced tumors have suggested that the virus may encode one or more direct-acting oncogenes. To date, however, no MDV-specific tumor antigens or candidate transforming genes have been demonstrated. In this paper, we report the identification of a MDV gene encoding a protein with homology to the leucine-zipper class of nuclear oncogenes. It also contains a proline-rich domain characteristic of another class of transcription factors. This gene, designated meq, maps to the long repeat of MDV and is one of the few genes that are highly expressed in MDV-induced T-cell tumors. To our knowledge, a herpesvirus gene closely related to the fos/jun family of oncogenes has not been reported previously.

Full text

PDF
4042

Images in this article

4043Image
on p.4043
4045Image
on p.4045
4045Image
on p.4045

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akiyama Y., Kato S. Two cell lines from lymphomas of Marek's disease. Biken J. 1974 Sep;17(3):105–116. [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bohmann D., Tjian R. Biochemical analysis of transcriptional activation by Jun: differential activity of c- and v-Jun. Cell. 1989 Nov 17;59(4):709–717. doi: 10.1016/0092-8674(89)90017-2. [DOI] [PubMed] [Google Scholar]
  4. Buckmaster A. E., Scott S. D., Sanderson M. J., Boursnell M. E., Ross N. L., Binns M. M. Gene sequence and mapping data from Marek's disease virus and herpesvirus of turkeys: implications for herpesvirus classification. J Gen Virol. 1988 Aug;69(Pt 8):2033–2042. doi: 10.1099/0022-1317-69-8-2033. [DOI] [PubMed] [Google Scholar]
  5. Cebrian J., Kaschka-Dierich C., Berthelot N., Sheldrick P. Inverted repeat nucleotide sequences in the genomes of Marek disease virus and the herpesvirus of the turkey. Proc Natl Acad Sci U S A. 1982 Jan;79(2):555–558. doi: 10.1073/pnas.79.2.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Countryman J., Jenson H., Seibl R., Wolf H., Miller G. Polymorphic proteins encoded within BZLF1 of defective and standard Epstein-Barr viruses disrupt latency. J Virol. 1987 Dec;61(12):3672–3679. doi: 10.1128/jvi.61.12.3672-3679.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deb S., Deb S. P. A 269-amino-acid segment with a pseudo-leucine zipper and a helix-turn-helix motif codes for the sequence-specific DNA-binding domain of herpes simplex virus type 1 origin-binding protein. J Virol. 1991 Jun;65(6):2829–2838. doi: 10.1128/jvi.65.6.2829-2838.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Farrell P. J., Rowe D. T., Rooney C. M., Kouzarides T. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO J. 1989 Jan;8(1):127–132. doi: 10.1002/j.1460-2075.1989.tb03356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fujiwara K. T., Ashida K., Nishina H., Iba H., Miyajima N., Nishizawa M., Kawai S. The chicken c-fos gene: cloning and nucleotide sequence analysis. J Virol. 1987 Dec;61(12):4012–4018. doi: 10.1128/jvi.61.12.4012-4018.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fukuchi K., Sudo M., Lee Y. S., Tanaka A., Nonoyama M. Structure of Marek's disease virus DNA: detailed restriction enzyme map. J Virol. 1984 Jul;51(1):102–109. doi: 10.1128/jvi.51.1.102-109.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Geelen J. L., Boom R., Klaver G. P., Minnaar R. P., Feltkamp M. C., van Milligen F. J., Sol C. J., van der Noordaa J. Transcriptional activation of the major immediate early transcription unit of human cytomegalovirus by heat-shock, arsenite and protein synthesis inhibitors. J Gen Virol. 1987 Nov;68(Pt 11):2925–2931. doi: 10.1099/0022-1317-68-11-2925. [DOI] [PubMed] [Google Scholar]
  13. Giam C. Z., Xu Y. L. HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element. J Biol Chem. 1989 Sep 15;264(26):15236–15241. [PubMed] [Google Scholar]
  14. Gibbs C. P., Nazerian K., Velicer L. F., Kung H. J. Extensive homology exists between Marek disease herpesvirus and its vaccine virus, herpesvirus of turkeys. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3365–3369. doi: 10.1073/pnas.81.11.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hai T., Curran T. Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3720–3724. doi: 10.1073/pnas.88.9.3720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Higgs D. R., Goodbourn S. E., Lamb J., Clegg J. B., Weatherall D. J., Proudfoot N. J. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature. 1983 Nov 24;306(5941):398–400. doi: 10.1038/306398a0. [DOI] [PubMed] [Google Scholar]
  17. Hirai K., Ikuta K., Kitamoto N., Kato S. Latency of herpesvirus of turkey and Marek's disease virus genomes in a chicken T-lymphoblastoid cell line. J Gen Virol. 1981 Mar;53(Pt 1):133–143. doi: 10.1099/0022-1317-53-1-133. [DOI] [PubMed] [Google Scholar]
  18. Hu J. C., O'Shea E. K., Kim P. S., Sauer R. T. Sequence requirements for coiled-coils: analysis with lambda repressor-GCN4 leucine zipper fusions. Science. 1990 Dec 7;250(4986):1400–1403. doi: 10.1126/science.2147779. [DOI] [PubMed] [Google Scholar]
  19. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  20. Lee H. S., Simon J. A., Lis J. T. Structure and expression of ubiquitin genes of Drosophila melanogaster. Mol Cell Biol. 1988 Nov;8(11):4727–4735. doi: 10.1128/mcb.8.11.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee K. A., Hai T. Y., SivaRaman L., Thimmappaya B., Hurst H. C., Jones N. C., Green M. R. A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355–8359. doi: 10.1073/pnas.84.23.8355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McKnight S. L., Kingsbury R. Transcriptional control signals of a eukaryotic protein-coding gene. Science. 1982 Jul 23;217(4557):316–324. doi: 10.1126/science.6283634. [DOI] [PubMed] [Google Scholar]
  23. Nagpal S., Ostrove J. M. Characterization of a potent varicella-zoster virus-encoded trans-repressor. J Virol. 1991 Oct;65(10):5289–5296. doi: 10.1128/jvi.65.10.5289-5296.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nazerian K., Elmubarak A., Sharma J. M. Establishment of B-lymphoblastoid cell lines from Marek's disease virus-induced tumors in turkeys. Int J Cancer. 1982 Jan 15;29(1):63–68. doi: 10.1002/ijc.2910290111. [DOI] [PubMed] [Google Scholar]
  25. Nazerian K., Stephens E. A., Sharma J. M., Lee L. F., Gailitis M., Witter R. L. A nonproducer T lymphoblastoid cell line from Marek's disease transplantable tumor (JMV). Avian Dis. 1977 Jan-Mar;21(1):69–76. [PubMed] [Google Scholar]
  26. Nazerian K., Witter R. L., Crittenden L. B., Noori-Dalloii M. R., Kung H. J. An IgM-producing B lymphoblastoid cell line established from lymphomas induced by a non-defective reticuloendotheliosis virus. J Gen Virol. 1982 Feb;58(Pt 2):351–360. doi: 10.1099/0022-1317-58-2-351. [DOI] [PubMed] [Google Scholar]
  27. Nishimura T., Vogt P. K. The avian cellular homolog of the oncogene jun. Oncogene. 1988 Dec;3(6):659–663. [PubMed] [Google Scholar]
  28. O'Shea E. K., Rutkowski R., Kim P. S. Evidence that the leucine zipper is a coiled coil. Science. 1989 Jan 27;243(4890):538–542. doi: 10.1126/science.2911757. [DOI] [PubMed] [Google Scholar]
  29. Phillips B., Abravaya K., Morimoto R. I. Analysis of the specificity and mechanism of transcriptional activation of the human hsp70 gene during infection by DNA viruses. J Virol. 1991 Nov;65(11):5680–5692. doi: 10.1128/jvi.65.11.5680-5692.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Roesler W. J., Vandenbark G. R., Hanson R. W. Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem. 1988 Jul 5;263(19):9063–9066. [PubMed] [Google Scholar]
  31. Ross L. J., Binns M. M., Pastorek J. DNA sequence and organization of genes in a 5.5 kbp EcoRI fragment mapping in the short unique segment of Marek's disease virus (strain RB1B). J Gen Virol. 1991 Apr;72(Pt 4):949–954. doi: 10.1099/0022-1317-72-4-949. [DOI] [PubMed] [Google Scholar]
  32. Ross L. J., Binns M. M. Properties and evolutionary relationships of the Marek's disease virus homologues of protein kinase, glycoprotein D and glycoprotein I of herpes simplex virus. J Gen Virol. 1991 Apr;72(Pt 4):939–947. doi: 10.1099/0022-1317-72-4-939. [DOI] [PubMed] [Google Scholar]
  33. Santomenna L. D., Colberg-Poley A. M. Induction of cellular hsp70 expression by human cytomegalovirus. J Virol. 1990 May;64(5):2033–2040. doi: 10.1128/jvi.64.5.2033-2040.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schat K. A., Buckmaster A., Ross L. J. Partial transcription map of Marek's disease herpesvirus in lytically infected cells and lymphoblastoid cell lines. Int J Cancer. 1989 Jul 15;44(1):101–109. doi: 10.1002/ijc.2910440119. [DOI] [PubMed] [Google Scholar]
  35. Schat K. A., Chen C. L., Calnek B. W., Char D. Transformation of T-lymphocyte subsets by Marek's disease herpesvirus. J Virol. 1991 Mar;65(3):1408–1413. doi: 10.1128/jvi.65.3.1408-1413.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  37. Silva R. F., Lee L. F. Monoclonal antibody-mediated immunoprecipitation of proteins from cells infected with Marek's disease virus or turkey herpesvirus. Virology. 1984 Jul 30;136(2):307–320. doi: 10.1016/0042-6822(84)90167-3. [DOI] [PubMed] [Google Scholar]
  38. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  39. Sugaya K., Bradley G., Nonoyama M., Tanaka A. Latent transcripts of Marek's disease virus are clustered in the short and long repeat regions. J Virol. 1990 Dec;64(12):5773–5782. doi: 10.1128/jvi.64.12.5773-5782.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wakakura M., Kennedy P. G., Foulds W. S., Clements G. B. Stress proteins accumulate in cultured retinal glial cells during herpes simplex viral infection. Exp Eye Res. 1987 Oct;45(4):557–567. doi: 10.1016/s0014-4835(87)80066-0. [DOI] [PubMed] [Google Scholar]
  42. Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]
  43. Witter R. L. Characteristics of Marek's disease viruses isolated from vaccinated commercial chicken flocks: association of viral pathotype with lymphoma frequency. Avian Dis. 1983 Jan-Mar;27(1):113–132. [PubMed] [Google Scholar]
  44. Witter R. L., Sharma J. M., Lee L. F., Opitz H. M., Henry C. W. Field trials to test the efficacy of polyvalent Marek's disease vaccines in broilers. Avian Dis. 1984 Jan-Mar;28(1):44–60. [PubMed] [Google Scholar]
  45. Xiao H., Lis J. T. Germline transformation used to define key features of heat-shock response elements. Science. 1988 Mar 4;239(4844):1139–1142. doi: 10.1126/science.3125608. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES