Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1987 Nov;61(11):3349–3355. doi: 10.1128/jvi.61.11.3349-3355.1987

The herpes simplex virus origins of DNA synthesis in the S component are each contained in a transcribed open reading frame.

J Hubenthal-Voss 1, L Starr 1, B Roizman 1
PMCID: PMC255928  PMID: 2822945

Abstract

In the herpes simplex virus 1 genome, the origins of viral DNA synthesis are located in the unique sequences of the L component (Oril) and in the reiterated sequences of the S component (OriS) located between the 5' terminus of the alpha 4 gene and the 5' terminus of either the alpha 22 (left terminus of the S component) or the alpha 47 (right terminus of the S component) gene. Studies prompted by the finding that only one, but not both, OriS sequence is dispensable for growth in cell culture indicate that each OriS sequence is contained in an open reading frame designated as OriSORF. The transcription of OriSORF is initiated approximately 860 nucleotides upstream from that of the alpha 4 gene and 162 nucleotides downstream, but on the opposite strand from the transcription initiation site of the alpha 22 or alpha 47 genes within the inverted repeat c sequence. The OriSORF transcript is 3' coterminal with the mRNA of the alpha 4 gene, polyadenylated but not spliced, transported into the cytoplasm, and capable of directing the synthesis of a 330-amino-acid protein with a translated molecular weight of approximately 34,000. Transcription is cycloheximide but not phosphonoacetate sensitive and is therefore regulated as either a beta or a gamma 1 gene. The implications of the transcription of OriS and of possible functions of the product of OriSORF are discussed.

Full text

PDF
3349

Images in this article

3351Image
on p.3351
3351Image
on p.3351

Selected References

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

  1. Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berg L., Lusky M., Stenlund A., Botchan M. R. Repression of bovine papilloma virus replication is mediated by a virally encoded trans-acting factor. Cell. 1986 Aug 29;46(5):753–762. doi: 10.1016/0092-8674(86)90351-x. [DOI] [PubMed] [Google Scholar]
  3. Campbell M. E., Palfreyman J. W., Preston C. M. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J Mol Biol. 1984 Nov 25;180(1):1–19. doi: 10.1016/0022-2836(84)90427-3. [DOI] [PubMed] [Google Scholar]
  4. Delius H., Clements J. B. A partial denaturation map of herpes simplex virus type 1 DNA: evidence for inversions of the unique DNA regions. J Gen Virol. 1976 Oct;33(1):125–133. doi: 10.1099/0022-1317-33-1-125. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Elias P., O'Donnell M. E., Mocarski E. S., Lehman I. R. A DNA binding protein specific for an origin of replication of herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6322–6326. doi: 10.1073/pnas.83.17.6322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  8. Hayward G. S., Jacob R. J., Wadsworth S. C., Roizman B. Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short components. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4243–4247. doi: 10.1073/pnas.72.11.4243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hubenthal-Voss J., Roizman B. Herpes simplex virus 1 reiterated S component sequences (c1) situated between the a sequence and alpha 4 gene are not essential for virus replication. J Virol. 1985 May;54(2):509–514. doi: 10.1128/jvi.54.2.509-514.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jenkins F. J., Howett M. K. Characterization of mRNAs that map in the BglII N fragment of the herpes simplex virus type 2 genome. J Virol. 1984 Oct;52(1):99–107. doi: 10.1128/jvi.52.1.99-107.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Longnecker R., Chatterjee S., Whitley R. J., Roizman B. Identification of a herpes simplex virus 1 glycoprotein gene within a gene cluster dispensable for growth in cell culture. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4303–4307. doi: 10.1073/pnas.84.12.4303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Longnecker R., Roizman B. Clustering of genes dispensable for growth in culture in the S component of the HSV-1 genome. Science. 1987 May 1;236(4801):573–576. doi: 10.1126/science.3033823. [DOI] [PubMed] [Google Scholar]
  15. Longnecker R., Roizman B. Generation of an inverting herpes simplex virus 1 mutant lacking the L-S junction a sequences, an origin of DNA synthesis, and several genes including those specifying glycoprotein E and the alpha 47 gene. J Virol. 1986 May;58(2):583–591. doi: 10.1128/jvi.58.2.583-591.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lusky M., Botchan M. R. Characterization of the bovine papilloma virus plasmid maintenance sequences. Cell. 1984 Feb;36(2):391–401. doi: 10.1016/0092-8674(84)90232-0. [DOI] [PubMed] [Google Scholar]
  17. Mackem S., Roizman B. Regulation of herpesvirus macromolecular synthesis: transcription-initiation sites and domains of alpha genes. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7122–7126. doi: 10.1073/pnas.77.12.7122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McGeoch D. J., Dolan A., Donald S., Brauer D. H. Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Res. 1986 Feb 25;14(4):1727–1745. doi: 10.1093/nar/14.4.1727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McGeoch D. J., Dolan A., Donald S., Rixon F. J. Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. J Mol Biol. 1985 Jan 5;181(1):1–13. doi: 10.1016/0022-2836(85)90320-1. [DOI] [PubMed] [Google Scholar]
  20. Mocarski E. S., Roizman B. Herpesvirus-dependent amplification and inversion of cell-associated viral thymidine kinase gene flanked by viral a sequences and linked to an origin of viral DNA replication. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5626–5630. doi: 10.1073/pnas.79.18.5626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morse L. S., Pereira L., Roizman B., Schaffer P. A. Anatomy of herpes simplex virus (HSV) DNA. X. Mapping of viral genes by analysis of polypeptides and functions specified by HSV-1 X HSV-2 recombinants. J Virol. 1978 May;26(2):389–410. doi: 10.1128/jvi.26.2.389-410.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. O'Hare P., Hayward G. S. Three trans-acting regulatory proteins of herpes simplex virus modulate immediate-early gene expression in a pathway involving positive and negative feedback regulation. J Virol. 1985 Dec;56(3):723–733. doi: 10.1128/jvi.56.3.723-733.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Orberg P. K., Schaffer P. A. Expression of herpes simplex virus type 1 major DNA-binding protein, ICP8, in transformed cell lines: complementation of deletion mutants and inhibition of wild-type virus. J Virol. 1987 Apr;61(4):1136–1146. doi: 10.1128/jvi.61.4.1136-1146.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Patel I., Bastia D. A replication origin is turned off by an origin-"silencer" sequence. Cell. 1986 Dec 5;47(5):785–792. doi: 10.1016/0092-8674(86)90521-0. [DOI] [PubMed] [Google Scholar]
  25. Pellett P. E., McKnight J. L., Jenkins F. J., Roizman B. Nucleotide sequence and predicted amino acid sequence of a protein encoded in a small herpes simplex virus DNA fragment capable of trans-inducing alpha genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870–5874. doi: 10.1073/pnas.82.17.5870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pizer L. I., Tedder D. G., Betz J. L., Wilcox K. W., Beard P. Regulation of transcription in vitro from herpes simplex virus genes. J Virol. 1986 Dec;60(3):950–959. doi: 10.1128/jvi.60.3.950-959.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Post L. E., Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. Cell. 1981 May;24(2):555–565. doi: 10.1016/0092-8674(81)90346-9. [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. Reisman D., Yates J., Sugden B. A putative origin of replication of plasmids derived from Epstein-Barr virus is composed of two cis-acting components. Mol Cell Biol. 1985 Aug;5(8):1822–1832. doi: 10.1128/mcb.5.8.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Roizman B., Spear P. G. Preparation of herpes simplex virus of high titer. J Virol. 1968 Jan;2(1):83–84. doi: 10.1128/jvi.2.1.83-84.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sample J., Hummel M., Braun D., Birkenbach M., Kieff E. Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5096–5100. doi: 10.1073/pnas.83.14.5096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sheldrick P., Berthelot N. Inverted repetitions in the chromosome of herpes simplex virus. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):667–678. doi: 10.1101/sqb.1974.039.01.080. [DOI] [PubMed] [Google Scholar]
  34. Staden R. Measurements of the effects that coding for a protein has on a DNA sequence and their use for finding genes. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):551–567. doi: 10.1093/nar/12.1part2.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stow N. D. Localization of an origin of DNA replication within the TRS/IRS repeated region of the herpes simplex virus type 1 genome. EMBO J. 1982;1(7):863–867. doi: 10.1002/j.1460-2075.1982.tb01261.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vlazny D. A., Frenkel N. Replication of herpes simplex virus DNA: localization of replication recognition signals within defective virus genomes. Proc Natl Acad Sci U S A. 1981 Feb;78(2):742–746. doi: 10.1073/pnas.78.2.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wadsworth S., Hayward G. S., Roizman B. Anatomy of herpes simplex virus DNA. V. Terminally repetitive sequences. J Virol. 1976 Feb;17(2):503–512. doi: 10.1128/jvi.17.2.503-512.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES