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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
. 1993 Oct 1;90(19):9056–9060. doi: 10.1073/pnas.90.19.9056

A herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution.

A Phelan 1, M Carmo-Fonseca 1, J McLaughlan 1, A I Lamond 1, J B Clements 1
PMCID: PMC47500  PMID: 8415652

Abstract

Herpes simplex virus 1 (HSV-1), a nuclear replicating DNA virus, has 73 identified genes of which only 4 contain introns. For this reason the virus probably makes only minimal use of the cellular RNA-splicing machinery. Antigens associated with the small nuclear ribonucleoprotein particles (snRNPs) that are subunits of splicing complexes have been reported to redistribute in the nucleus and become concentrated into the intranuclear structures, the interchromatin granules, after HSV-1 infection [Martin, T. E., Barghusen, S. C., Leser, G. P. & Spear, P. G. (1987) J. Cell Biol. 105, 2069-2082]. We observe this snRNP redistribution upon HSV-1 infection, in which the widespread snRNP staining pattern changes to a restricted punctate distribution with a concomitant loss of coiled bodies in HSV-1-infected cells. We show here that expression of the immediate-early (IE) subset of HSV-1 genes is necessary and sufficient for snRNP redistribution. Using a series of HSV-1 mutants in different IE genes, we have established that specifically the product of the viral IE63 (ICP27) gene is essential for this effect, and transfection experiments revealed that IE63 expression alone can cause the snRNP redistribution. Further, we show that the IE63 gene product colocalizes with the redistributed snRNP in the nucleus. The snRNP redistribution caused by HSV-1 infection resembles the effect seen after inhibition of transcription in uninfected cells. In HSV-1-infected cells, however, the snRNP redistribution is under the control of viral IE gene products and occurs during active virus gene transcription.

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Selected References

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  1. Andrade L. E., Chan E. K., Raska I., Peebles C. L., Roos G., Tan E. M. Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin. J Exp Med. 1991 Jun 1;173(6):1407–1419. doi: 10.1084/jem.173.6.1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carmo-Fonseca M., Pepperkok R., Carvalho M. T., Lamond A. I. Transcription-dependent colocalization of the U1, U2, U4/U6, and U5 snRNPs in coiled bodies. J Cell Biol. 1992 Apr;117(1):1–14. doi: 10.1083/jcb.117.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carmo-Fonseca M., Pepperkok R., Sproat B. S., Ansorge W., Swanson M. S., Lamond A. I. In vivo detection of snRNP-rich organelles in the nuclei of mammalian cells. EMBO J. 1991 Jul;10(7):1863–1873. doi: 10.1002/j.1460-2075.1991.tb07712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carmo-Fonseca M., Tollervey D., Pepperkok R., Barabino S. M., Merdes A., Brunner C., Zamore P. D., Green M. R., Hurt E., Lamond A. I. Mammalian nuclei contain foci which are highly enriched in components of the pre-mRNA splicing machinery. EMBO J. 1991 Jan;10(1):195–206. doi: 10.1002/j.1460-2075.1991.tb07936.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fey E. G., Krochmalnic G., Penman S. The nonchromatin substructures of the nucleus: the ribonucleoprotein (RNP)-containing and RNP-depleted matrices analyzed by sequential fractionation and resinless section electron microscopy. J Cell Biol. 1986 May;102(5):1654–1665. doi: 10.1083/jcb.102.5.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Green M. R. Biochemical mechanisms of constitutive and regulated pre-mRNA splicing. Annu Rev Cell Biol. 1991;7:559–599. doi: 10.1146/annurev.cb.07.110191.003015. [DOI] [PubMed] [Google Scholar]
  7. Habets W. J., Hoet M. H., De Jong B. A., Van der Kemp A., Van Venrooij W. J. Mapping of B cell epitopes on small nuclear ribonucleoproteins that react with human autoantibodies as well as with experimentally-induced mouse monoclonal antibodies. J Immunol. 1989 Oct 15;143(8):2560–2566. [PubMed] [Google Scholar]
  8. Lerner E. A., Lerner M. R., Janeway C. A., Jr, Steitz J. A. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc Natl Acad Sci U S A. 1981 May;78(5):2737–2741. doi: 10.1073/pnas.78.5.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marsden H. S., Crombie I. K., Subak-Sharpe J. H. Control of protein synthesis in herpesvirus-infected cells: analysis of the polypeptides induced by wild type and sixteen temperature-sensitive mutants of HSV strain 17. J Gen Virol. 1976 Jun;31(3):347–372. doi: 10.1099/0022-1317-31-3-347. [DOI] [PubMed] [Google Scholar]
  10. Martin T. E., Barghusen S. C., Leser G. P., Spear P. G. Redistribution of nuclear ribonucleoprotein antigens during herpes simplex virus infection. J Cell Biol. 1987 Nov;105(5):2069–2082. doi: 10.1083/jcb.105.5.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mavromara-Nazos P., Ackermann M., Roizman B. Construction and properties of a viable herpes simplex virus 1 recombinant lacking coding sequences of the alpha 47 gene. J Virol. 1986 Nov;60(2):807–812. doi: 10.1128/jvi.60.2.807-812.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McLauchlan J., Phelan A., Loney C., Sandri-Goldin R. M., Clements J. B. Herpes simplex virus IE63 acts at the posttranscriptional level to stimulate viral mRNA 3' processing. J Virol. 1992 Dec;66(12):6939–6945. doi: 10.1128/jvi.66.12.6939-6945.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pruijn G. J., Slobbe R. L., Van Venrooij W. J. Structure and function of La and Ro RNPs. Mol Biol Rep. 1990;14(2-3):43–48. doi: 10.1007/BF00360410. [DOI] [PubMed] [Google Scholar]
  14. Sacks W. R., Greene C. C., Aschman D. P., Schaffer P. A. Herpes simplex virus type 1 ICP27 is an essential regulatory protein. J Virol. 1985 Sep;55(3):796–805. doi: 10.1128/jvi.55.3.796-805.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sandri-Goldin R. M., Mendoza G. E. A herpesvirus regulatory protein appears to act post-transcriptionally by affecting mRNA processing. Genes Dev. 1992 May;6(5):848–863. doi: 10.1101/gad.6.5.848. [DOI] [PubMed] [Google Scholar]
  16. Sears A. E., Halliburton I. W., Meignier B., Silver S., Roizman B. Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice. J Virol. 1985 Aug;55(2):338–346. doi: 10.1128/jvi.55.2.338-346.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sekulovich R. E., Leary K., Sandri-Goldin R. M. The herpes simplex virus type 1 alpha protein ICP27 can act as a trans-repressor or a trans-activator in combination with ICP4 and ICP0. J Virol. 1988 Dec;62(12):4510–4522. doi: 10.1128/jvi.62.12.4510-4522.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sharp P. A. Splicing of messenger RNA precursors. Science. 1987 Feb 13;235(4790):766–771. doi: 10.1126/science.3544217. [DOI] [PubMed] [Google Scholar]
  19. Smith I. L., Hardwicke M. A., Sandri-Goldin R. M. Evidence that the herpes simplex virus immediate early protein ICP27 acts post-transcriptionally during infection to regulate gene expression. Virology. 1992 Jan;186(1):74–86. doi: 10.1016/0042-6822(92)90062-t. [DOI] [PubMed] [Google Scholar]
  20. Stow N. D., Stow E. C. Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol. 1986 Dec;67(Pt 12):2571–2585. doi: 10.1099/0022-1317-67-12-2571. [DOI] [PubMed] [Google Scholar]

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