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. 1997 Feb;71(2):1133–1139. doi: 10.1128/jvi.71.2.1133-1139.1997

Association of herpes simplex virus regulatory protein ICP22 with transcriptional complexes containing EAP, ICP4, RNA polymerase II, and viral DNA requires posttranslational modification by the U(L)13 proteinkinase.

R Leopardi 1, P L Ward 1, W O Ogle 1, B Roizman 1
PMCID: PMC191165  PMID: 8995634

Abstract

The expression of herpes simplex virus 1 gamma (late) genes requires functional alpha proteins (gamma1 genes) and the onset of viral DNA synthesis (gamma2 genes). We report that late in infection after the onset of viral DNA synthesis, cell nuclei exhibit defined structures which contain two viral regulatory proteins (infected cell proteins 4 and 22) required for gamma gene expression, RNA polymerase II, a host nucleolar protein (EAP or L22) known to be associated with ribosomes and to bind small RNAs, including the Epstein-Barr virus small nuclear RNAs, and newly synthesized progeny DNA. The formation of these complexes required the onset of viral DNA synthesis. The association of infected cell protein 22, a highly posttranslationally processed protein, with these structures did not occur in cells infected with a viral mutant deleted in the genes U(L)13 and U(S)3, each of which specifies a protein kinase known to phosphorylate the protein.

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Selected References

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  1. Ackermann M., Sarmiento M., Roizman B. Application of antibody to synthetic peptides for characterization of the intact and truncated alpha 22 protein specified by herpes simplex virus 1 and the R325 alpha 22- deletion mutant. J Virol. 1985 Oct;56(1):207–215. doi: 10.1128/jvi.56.1.207-215.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blaho J. A., Mitchell C., Roizman B. Guanylylation and adenylylation of the alpha regulatory proteins of herpes simplex virus require a viral beta or gamma function. J Virol. 1993 Jul;67(7):3891–3900. doi: 10.1128/jvi.67.7.3891-3900.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carter K. L., Roizman B. The promoter and transcriptional unit of a novel herpes simplex virus 1 alpha gene are contained in, and encode a protein in frame with, the open reading frame of the alpha 22 gene. J Virol. 1996 Jan;70(1):172–178. doi: 10.1128/jvi.70.1.172-178.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Costanzo F., Campadelli-Fiume G., Foa-Tomasi L., Cassai E. Evidence that herpes simplex virus DNA is transcribed by cellular RNA polymerase B. J Virol. 1977 Mar;21(3):996–1001. doi: 10.1128/jvi.21.3.996-1001.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DeLuca N. A., McCarthy A. M., Schaffer P. A. Isolation and characterization of deletion mutants of herpes simplex virus type 1 in the gene encoding immediate-early regulatory protein ICP4. J Virol. 1985 Nov;56(2):558–570. doi: 10.1128/jvi.56.2.558-570.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DiDonato J. A., Muller M. T. DNA binding and gene regulation by the herpes simplex virus type 1 protein ICP4 and involvement of the TATA element. J Virol. 1989 Sep;63(9):3737–3747. doi: 10.1128/jvi.63.9.3737-3747.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ejercito P. M., Kieff E. D., Roizman B. Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol. 1968 May;2(3):357–364. doi: 10.1099/0022-1317-2-3-357. [DOI] [PubMed] [Google Scholar]
  8. Everett R. D., Maul G. G. HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J. 1994 Nov 1;13(21):5062–5069. doi: 10.1002/j.1460-2075.1994.tb06835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Faber S. W., Wilcox K. W. Association of the herpes simplex virus regulatory protein ICP4 with specific nucleotide sequences in DNA. Nucleic Acids Res. 1986 Aug 11;14(15):6067–6083. doi: 10.1093/nar/14.15.6067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Godowski P. J., Knipe D. M. Identification of a herpes simplex virus function that represses late gene expression from parental viral genomes. J Virol. 1985 Aug;55(2):357–365. doi: 10.1128/jvi.55.2.357-365.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis requires functional viral polypeptides. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1276–1280. doi: 10.1073/pnas.72.4.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacob R. J., Morse L. S., Roizman B. Anatomy of herpes simplex virus DNA. XII. Accumulation of head-to-tail concatemers in nuclei of infected cells and their role in the generation of the four isomeric arrangements of viral DNA. J Virol. 1979 Feb;29(2):448–457. doi: 10.1128/jvi.29.2.448-457.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacob R. J., Roizman B. Anatomy of herpes simplex virus DNA VIII. Properties of the replicating DNA. J Virol. 1977 Aug;23(2):394–411. doi: 10.1128/jvi.23.2.394-411.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Knipe D. M., Senechek D., Rice S. A., Smith J. L. Stages in the nuclear association of the herpes simplex virus transcriptional activator protein ICP4. J Virol. 1987 Feb;61(2):276–284. doi: 10.1128/jvi.61.2.276-284.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kristie T. M., Roizman B. Alpha 4, the major regulatory protein of herpes simplex virus type 1, is stably and specifically associated with promoter-regulatory domains of alpha genes and of selected other viral genes. Proc Natl Acad Sci U S A. 1986 May;83(10):3218–3222. doi: 10.1073/pnas.83.10.3218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kristie T. M., Roizman B. DNA-binding site of major regulatory protein alpha 4 specifically associated with promoter-regulatory domains of alpha genes of herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4700–4704. doi: 10.1073/pnas.83.13.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuddus R., Gu B., DeLuca N. A. Relationship between TATA-binding protein and herpes simplex virus type 1 ICP4 DNA-binding sites in complex formation and repression of transcription. J Virol. 1995 Sep;69(9):5568–5575. doi: 10.1128/jvi.69.9.5568-5575.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Leopardi R., Michael N., Roizman B. Repression of the herpes simplex virus 1 alpha 4 gene by its gene product (ICP4) within the context of the viral genome is conditioned by the distance and stereoaxial alignment of the ICP4 DNA binding site relative to the TATA box. J Virol. 1995 May;69(5):3042–3048. doi: 10.1128/jvi.69.5.3042-3048.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Leopardi R., Roizman B. Functional interaction and colocalization of the herpes simplex virus 1 major regulatory protein ICP4 with EAP, a nucleolar-ribosomal protein. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4572–4576. doi: 10.1073/pnas.93.10.4572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Maul G. G., Guldner H. H., Spivack J. G. Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J Gen Virol. 1993 Dec;74(Pt 12):2679–2690. doi: 10.1099/0022-1317-74-12-2679. [DOI] [PubMed] [Google Scholar]
  23. Michael N., Roizman B. Binding of the herpes simplex virus major regulatory protein to viral DNA. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9808–9812. doi: 10.1073/pnas.86.24.9808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Michael N., Roizman B. Repression of the herpes simplex virus 1 alpha 4 gene by its gene product occurs within the context of the viral genome and is associated with all three identified cognate sites. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2286–2290. doi: 10.1073/pnas.90.6.2286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Michael N., Spector D., Mavromara-Nazos P., Kristie T. M., Roizman B. The DNA-binding properties of the major regulatory protein alpha 4 of herpes simplex viruses. Science. 1988 Mar 25;239(4847):1531–1534. doi: 10.1126/science.2832940. [DOI] [PubMed] [Google Scholar]
  26. Muller M. T. Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site. J Virol. 1987 Mar;61(3):858–865. doi: 10.1128/jvi.61.3.858-865.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Post L. E., Roizman B. A generalized technique for deletion of specific genes in large genomes: alpha gene 22 of herpes simplex virus 1 is not essential for growth. Cell. 1981 Jul;25(1):227–232. doi: 10.1016/0092-8674(81)90247-6. [DOI] [PubMed] [Google Scholar]
  28. Preston C. M. Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. J Virol. 1979 Jan;29(1):275–284. doi: 10.1128/jvi.29.1.275-284.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Purves F. C., Ogle W. O., Roizman B. Processing of the herpes simplex virus regulatory protein alpha 22 mediated by the UL13 protein kinase determines the accumulation of a subset of alpha and gamma mRNAs and proteins in infected cells. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6701–6705. doi: 10.1073/pnas.90.14.6701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Purves F. C., Roizman B. The UL13 gene of herpes simplex virus 1 encodes the functions for posttranslational processing associated with phosphorylation of the regulatory protein alpha 22. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7310–7314. doi: 10.1073/pnas.89.16.7310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Quinlan M. P., Chen L. B., Knipe D. M. The intranuclear location of a herpes simplex virus DNA-binding protein is determined by the status of viral DNA replication. Cell. 1984 Apr;36(4):857–868. doi: 10.1016/0092-8674(84)90035-7. [DOI] [PubMed] [Google Scholar]
  32. ROIZMAN B., ROANE P. R., Jr THE MULTIPLICATION OF HERPES SIMPLEX VIRUS. II. THE RELATION BETWEEN PROTEIN SYNTHESIS AND THE DUPLICATION OF VIRAL DNA IN INFECTED HEP-2 CELLS. Virology. 1964 Feb;22:262–269. doi: 10.1016/0042-6822(64)90011-x. [DOI] [PubMed] [Google Scholar]
  33. Randall R. E., Dinwoodie N. Intranuclear localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol. 1986 Oct;67(Pt 10):2163–2177. doi: 10.1099/0022-1317-67-10-2163. [DOI] [PubMed] [Google Scholar]
  34. Rice S. A., Long M. C., Lam V., Schaffer P. A., Spencer C. A. Herpes simplex virus immediate-early protein ICP22 is required for viral modification of host RNA polymerase II and establishment of the normal viral transcription program. J Virol. 1995 Sep;69(9):5550–5559. doi: 10.1128/jvi.69.9.5550-5559.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rice S. A., Long M. C., Lam V., Spencer C. A. RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection. J Virol. 1994 Feb;68(2):988–1001. doi: 10.1128/jvi.68.2.988-1001.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Shepard A. A., DeLuca N. A. A second-site revertant of a defective herpes simplex virus ICP4 protein with restored regulatory activities and impaired DNA-binding properties. J Virol. 1991 Feb;65(2):787–795. doi: 10.1128/jvi.65.2.787-795.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Smith C. A., Bates P., Rivera-Gonzalez R., Gu B., DeLuca N. A. ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. J Virol. 1993 Aug;67(8):4676–4687. doi: 10.1128/jvi.67.8.4676-4687.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Toczyski D. P., Matera A. G., Ward D. C., Steitz J. A. The Epstein-Barr virus (EBV) small RNA EBER1 binds and relocalizes ribosomal protein L22 in EBV-infected human B lymphocytes. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3463–3467. doi: 10.1073/pnas.91.8.3463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Toczyski D. P., Steitz J. A. EAP, a highly conserved cellular protein associated with Epstein-Barr virus small RNAs (EBERs). EMBO J. 1991 Feb;10(2):459–466. doi: 10.1002/j.1460-2075.1991.tb07968.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Toczyski D. P., Steitz J. A. The cellular RNA-binding protein EAP recognizes a conserved stem-loop in the Epstein-Barr virus small RNA EBER 1. Mol Cell Biol. 1993 Jan;13(1):703–710. doi: 10.1128/mcb.13.1.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ward P. L., Ogle W. O., Roizman B. Assemblons: nuclear structures defined by aggregation of immature capsids and some tegument proteins of herpes simplex virus 1. J Virol. 1996 Jul;70(7):4623–4631. doi: 10.1128/jvi.70.7.4623-4631.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. de Bruyn Kops A., Knipe D. M. Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein. Cell. 1988 Dec 2;55(5):857–868. doi: 10.1016/0092-8674(88)90141-9. [DOI] [PubMed] [Google Scholar]
  44. de Bruyn Kops A., Knipe D. M. Preexisting nuclear architecture defines the intranuclear location of herpesvirus DNA replication structures. J Virol. 1994 Jun;68(6):3512–3526. doi: 10.1128/jvi.68.6.3512-3526.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]

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