Abstract
Marek's disease virus (MDV) latency-associated transcripts include at least two MDV small RNAs (MSRs) and a 10-kb RNA which map antisense to the ICP4 homolog gene and are relatively abundant in MDV-transformed lymphoblastoid cells. This report further describes the biological and structural properties of these RNAs. First, these RNAs were detected in primary lymphomas isolated from chickens infected with several oncogenic MDV strains. Second, the MSRs are nonpolyadenylated, whereas, the 10-kb RNA is predominantly polyadenylated. Third, MSRs localize to the nuclei of both lymphoblastoid cells and cytolytically infected chicken embryo fibroblasts. Fourth, the 3'-region splice junctions of the MSRs during latent and productive infection were determined by sequencing RNA-PCR products generated with primers that flank the 3' splice region. The MSRs contain at least three introns, the largest of which overlaps the ICP4 putative translational start site. Fifth, the 5' end of the MSRs initiates approximately 5 kb upstream from the main body of the RNA. The extreme 5' exon is approximately 251 nucleotides (nt) long and is joined to the main body of the transcript upon removal of a 4,852-nt intron. Finally, the 10-kb RNA lies entirely within the repeats flanking the unique short region of the genome. We believe that the MSRs and 10-kb RNA belong to a family of spliced RNAs that map antisense to the ICP4 gene and comprise a complex transcriptional unit expressed during MDV-induced T-cell transformation.
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- Anderson A. S., Francesconi A., Morgan R. W. Complete nucleotide sequence of the Marek's disease virus ICP4 gene. Virology. 1992 Aug;189(2):657–667. doi: 10.1016/0042-6822(92)90589-h. [DOI] [PubMed] [Google Scholar]
- Batchelor A. H., O'Hare P. Regulation and cell-type-specific activity of a promoter located upstream of the latency-associated transcript of herpes simplex virus type 1. J Virol. 1990 Jul;64(7):3269–3279. doi: 10.1128/jvi.64.7.3269-3279.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
- Brunovskis P., Velicer L. F. The Marek's disease virus (MDV) unique short region: alphaherpesvirus-homologous, fowlpox virus-homologous, and MDV-specific genes. Virology. 1995 Jan 10;206(1):324–338. doi: 10.1016/s0042-6822(95)80048-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Calnek B. W. Marek's disease--a model for herpesvirus oncology. Crit Rev Microbiol. 1986;12(4):293–320. doi: 10.3109/10408418509104432. [DOI] [PubMed] [Google Scholar]
- Cantello J. L., Anderson A. S., Morgan R. W. Identification of latency-associated transcripts that map antisense to the ICP4 homolog gene of Marek's disease virus. J Virol. 1994 Oct;68(10):6280–6290. doi: 10.1128/jvi.68.10.6280-6290.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Chen X. B., Sondermeijer P. J., Velicer L. F. Identification of a unique Marek's disease virus gene which encodes a 38-kilodalton phosphoprotein and is expressed in both lytically infected cells and latently infected lymphoblastoid tumor cells. J Virol. 1992 Jan;66(1):85–94. doi: 10.1128/jvi.66.1.85-94.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheung A. K. Cloning of the latency gene and the early protein 0 gene of pseudorabies virus. J Virol. 1991 Oct;65(10):5260–5271. doi: 10.1128/jvi.65.10.5260-5271.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Croen K. D., Ostrove J. M., Dragovic L. J., Smialek J. E., Straus S. E. Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene "anti-sense" transcript by in situ hybridization. N Engl J Med. 1987 Dec 3;317(23):1427–1432. doi: 10.1056/NEJM198712033172302. [DOI] [PubMed] [Google Scholar]
- Cui Z. Z., Lee L. F., Liu J. L., Kung H. J. Structural analysis and transcriptional mapping of the Marek's disease virus gene encoding pp38, an antigen associated with transformed cells. J Virol. 1991 Dec;65(12):6509–6515. doi: 10.1128/jvi.65.12.6509-6515.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Devi-Rao G. B., Goodart S. A., Hecht L. M., Rochford R., Rice M. K., Wagner E. K. Relationship between polyadenylated and nonpolyadenylated herpes simplex virus type 1 latency-associated transcripts. J Virol. 1991 May;65(5):2179–2190. doi: 10.1128/jvi.65.5.2179-2190.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farrell M. J., Dobson A. T., Feldman L. T. Herpes simplex virus latency-associated transcript is a stable intron. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):790–794. doi: 10.1073/pnas.88.3.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kristie T. M., Roizman B. Host cell proteins bind to the cis-acting site required for virion-mediated induction of herpes simplex virus 1 alpha genes. Proc Natl Acad Sci U S A. 1987 Jan;84(1):71–75. doi: 10.1073/pnas.84.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lagunoff M., Roizman B. The regulation of synthesis and properties of the protein product of open reading frame P of the herpes simplex virus 1 genome. J Virol. 1995 Jun;69(6):3615–3623. doi: 10.1128/jvi.69.6.3615-3623.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li D. S., Pastorek J., Zelník V., Smith G. D., Ross L. J. Identification of novel transcripts complementary to the Marek's disease virus homologue of the ICP4 gene of herpes simplex virus. J Gen Virol. 1994 Jul;75(Pt 7):1713–1722. doi: 10.1099/0022-1317-75-7-1713. [DOI] [PubMed] [Google Scholar]
- McKie E. A., Ubukata E., Hasegawa S., Zhang S., Nonoyama M., Tanaka A. The transcripts from the sequences flanking the short component of Marek's disease virus during latent infection form a unique family of 3'-coterminal RNAs. J Virol. 1995 Feb;69(2):1310–1314. doi: 10.1128/jvi.69.2.1310-1314.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moriuchi H., Moriuchi M., Cohen J. I. Proteins and cis-acting elements associated with transactivation of the varicella-zoster virus (VZV) immediate-early gene 62 promoter by VZV open reading frame 10 protein. J Virol. 1995 Aug;69(8):4693–4701. doi: 10.1128/jvi.69.8.4693-4701.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
- Nicosia M., Zabolotny J. M., Lirette R. P., Fraser N. W. The HSV-1 2-kb latency-associated transcript is found in the cytoplasm comigrating with ribosomal subunits during productive infection. Virology. 1994 Nov 1;204(2):717–728. doi: 10.1006/viro.1994.1587. [DOI] [PubMed] [Google Scholar]
- Parcells M. S., Anderson A. S., Morgan T. W. Retention of oncogenicity by a Marek's disease virus mutant lacking six unique short region genes. J Virol. 1995 Dec;69(12):7888–7898. doi: 10.1128/jvi.69.12.7888-7898.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Priola S. A., Gustafson D. P., Wagner E. K., Stevens J. G. A major portion of the latent pseudorabies virus genome is transcribed in trigeminal ganglia of pigs. J Virol. 1990 Oct;64(10):4755–4760. doi: 10.1128/jvi.64.10.4755-4760.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Priola S. A., Stevens J. G. The 5' and 3' limits of transcription in the pseudorabies virus latency associated transcription unit. Virology. 1991 Jun;182(2):852–856. doi: 10.1016/0042-6822(91)90628-o. [DOI] [PubMed] [Google Scholar]
- Rock D. L., Beam S. L., Mayfield J. E. Mapping bovine herpesvirus type 1 latency-related RNA in trigeminal ganglia of latently infected rabbits. J Virol. 1987 Dec;61(12):3827–3831. doi: 10.1128/jvi.61.12.3827-3831.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rock D. L., Hagemoser W. A., Osorio F. A., Reed D. E. Detection of bovine herpesvirus type 1 RNA in trigeminal ganglia of latently infected rabbits by in situ hybridization. J Gen Virol. 1986 Nov;67(Pt 11):2515–2520. doi: 10.1099/0022-1317-67-11-2515. [DOI] [PubMed] [Google Scholar]
- 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]
- Sakaguchi M., Urakawa T., Hirayama Y., Miki N., Yamamoto M., Hirai K. Sequence determination and genetic content of an 8.9-kb restriction fragment in the short unique region and the internal inverted repeat of Marek's disease virus type 1 DNA. Virus Genes. 1992 Nov;6(4):365–378. doi: 10.1007/BF01703085. [DOI] [PubMed] [Google Scholar]
- Shek W. R., Calnek B. W., Schat K. A., Chen C. H. Characterization of Marek's disease virus-infected lymphocytes: discrimination between cytolytically and latently infected cells. J Natl Cancer Inst. 1983 Mar;70(3):485–491. [PubMed] [Google Scholar]
- Stevens J. G., Wagner E. K., Devi-Rao G. B., Cook M. L., Feldman L. T. RNA complementary to a herpesvirus alpha gene mRNA is prominent in latently infected neurons. Science. 1987 Feb 27;235(4792):1056–1059. doi: 10.1126/science.2434993. [DOI] [PubMed] [Google Scholar]
- Wagner E. K., Flanagan W. M., Devi-Rao G., Zhang Y. F., Hill J. M., Anderson K. P., Stevens J. G. The herpes simplex virus latency-associated transcript is spliced during the latent phase of infection. J Virol. 1988 Dec;62(12):4577–4585. doi: 10.1128/jvi.62.12.4577-4585.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zwaagstra J. C., Ghiasi H., Nesburn A. B., Wechsler S. L. Identification of a major regulatory sequence in the latency associated transcript (LAT) promoter of herpes simplex virus type 1 (HSV-1). Virology. 1991 May;182(1):287–297. doi: 10.1016/0042-6822(91)90672-x. [DOI] [PubMed] [Google Scholar]
- Zwaagstra J. C., Ghiasi H., Slanina S. M., Nesburn A. B., Wheatley S. C., Lillycrop K., Wood J., Latchman D. S., Patel K., Wechsler S. L. Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript. J Virol. 1990 Oct;64(10):5019–5028. doi: 10.1128/jvi.64.10.5019-5028.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]