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. 1995 Sep;69(9):5560–5567. doi: 10.1128/jvi.69.9.5560-5567.1995

Pseudorabies virus and equine herpesvirus 1 share a nonessential gene which is absent in other herpesviruses and located adjacent to a highly conserved gene cluster.

J Baumeister 1, B G Klupp 1, T C Mettenleiter 1
PMCID: PMC189410  PMID: 7637001

Abstract

We have determined the nucleotide sequence and transcriptional pattern of a group of open reading frames in the pseudorabies virus (PrV) genome located near the left end of the unique long region within BamHI 5' fragment at map positions 0.01 to 0.06. The 7,412-bp BamHI 5' fragment was found to contain five complete open reading frames and part of a sixth whose deduced amino acid sequences showed homology to the UL50 (partial), UL51, UL52, UL53, and UL54 gene products of herpes simplex virus type 1 (HSV-1) and corresponding genes identified in other alphaherpesviruses. Homologs to the UL55 and UL56 genes of HSV-1 were not detected. However, we identified a gene with homology only to the first open reading frame (ORF-1) of the equine herpesvirus 1 strain Ab4 (E. A. Telford, M. S. Watson, K. McBride, and A. J. Davison, Virology 189:304-316, 1992). Northern blot analyses revealed unique mRNAs for the UL51, UL54, and ORF-1 genes and a set of 3'-coterminal mRNAs for the UL52 to UL54 genes. A PrV mutant lacking ORF-1 was isolated after deletion of ORF-1 coding sequences and insertion of a lacZ expression cassette. The ORF-1- PrV mutant was able to productively replicate in noncomplementing cells to levels similar to those of wild-type PrV, proving that ORF-1 is not essential for replication of PrV in cell culture. The conservation of this gene between PrV and equine herpesvirus 1 documents the close evolutionary relationship between these animal herpesviruses and points to a possible function of the respective proteins in infection of the natural host.

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Selected References

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  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  2. Barker D. E., Roizman B. Identification of three genes nonessential for growth in cell culture near the right terminus of the unique sequences of long component of herpes simplex virus 1. Virology. 1990 Aug;177(2):684–691. doi: 10.1016/0042-6822(90)90534-x. [DOI] [PubMed] [Google Scholar]
  3. Ben-Porat T., Veach R. A., Ihara S. Localization of the regions of homology between the genomes of herpes simplex virus, type 1, and pseudorabies virus. Virology. 1983 May;127(1):194–204. doi: 10.1016/0042-6822(83)90383-5. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  6. Briggs M. R., Kadonaga J. T., Bell S. P., Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. doi: 10.1126/science.3529394. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Chee M. S., Bankier A. T., Beck S., Bohni R., Brown C. M., Cerny R., Horsnell T., Hutchison C. A., 3rd, Kouzarides T., Martignetti J. A. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–169. doi: 10.1007/978-3-642-74980-3_6. [DOI] [PubMed] [Google Scholar]
  10. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  11. Corden J., Wasylyk B., Buchwalder A., Sassone-Corsi P., Kedinger C., Chambon P. Promoter sequences of eukaryotic protein-coding genes. Science. 1980 Sep 19;209(4463):1406–1414. doi: 10.1126/science.6251548. [DOI] [PubMed] [Google Scholar]
  12. Crute J. J., Tsurumi T., Zhu L. A., Weller S. K., Olivo P. D., Challberg M. D., Mocarski E. S., Lehman I. R. Herpes simplex virus 1 helicase-primase: a complex of three herpes-encoded gene products. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2186–2189. doi: 10.1073/pnas.86.7.2186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  14. Dean H. J., Cheung A. K. A 3' coterminal gene cluster in pseudorabies virus contains herpes simplex virus UL1, UL2, and UL3 gene homologs and a unique UL3.5 open reading frame. J Virol. 1993 Oct;67(10):5955–5961. doi: 10.1128/jvi.67.10.5955-5961.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dean H. J., Cheung A. K. Identification of the pseudorabies virus UL4 and UL5 (helicase) genes. Virology. 1994 Aug 1;202(2):962–967. doi: 10.1006/viro.1994.1419. [DOI] [PubMed] [Google Scholar]
  16. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dolter K. E., Ramaswamy R., Holland T. C. Syncytial mutations in the herpes simplex virus type 1 gK (UL53) gene occur in two distinct domains. J Virol. 1994 Dec;68(12):8277–8281. doi: 10.1128/jvi.68.12.8277-8281.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fisher F. B., Preston V. G. Isolation and characterisation of herpes simplex virus type 1 mutants which fail to induce dUTPase activity. Virology. 1986 Jan 15;148(1):190–197. doi: 10.1016/0042-6822(86)90414-9. [DOI] [PubMed] [Google Scholar]
  19. Fitzgerald M., Shenk T. The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs. Cell. 1981 Apr;24(1):251–260. doi: 10.1016/0092-8674(81)90521-3. [DOI] [PubMed] [Google Scholar]
  20. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  21. Hardwicke M. A., Vaughan P. J., Sekulovich R. E., O'Conner R., Sandri-Goldin R. M. The regions important for the activator and repressor functions of herpes simplex virus type 1 alpha protein ICP27 map to the C-terminal half of the molecule. J Virol. 1989 Nov;63(11):4590–4602. doi: 10.1128/jvi.63.11.4590-4602.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  23. Hutchinson L., Goldsmith K., Snoddy D., Ghosh H., Graham F. L., Johnson D. C. Identification and characterization of a novel herpes simplex virus glycoprotein, gK, involved in cell fusion. J Virol. 1992 Sep;66(9):5603–5609. doi: 10.1128/jvi.66.9.5603-5609.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hutchinson L., Graham F. L., Cai W., Debroy C., Person S., Johnson D. C. Herpes simplex virus (HSV) glycoproteins B and K inhibit cell fusion induced by HSV syncytial mutants. Virology. 1993 Oct;196(2):514–531. doi: 10.1006/viro.1993.1507. [DOI] [PubMed] [Google Scholar]
  25. Ihara S., Feldman L., Watanabe S., Ben-Porat T. Characterization of the immediate-early functions of pseudorabies virus. Virology. 1983 Dec;131(2):437–454. doi: 10.1016/0042-6822(83)90510-x. [DOI] [PubMed] [Google Scholar]
  26. KAPLAN A. S., VATTER A. E. A comparison of herpes simplex and pseudorabies viruses. Virology. 1959 Apr;7(4):394–407. doi: 10.1016/0042-6822(59)90068-6. [DOI] [PubMed] [Google Scholar]
  27. Klinedinst D. K., Challberg M. D. Helicase-primase complex of herpes simplex virus type 1: a mutation in the UL52 subunit abolishes primase activity. J Virol. 1994 Jun;68(6):3693–3701. doi: 10.1128/jvi.68.6.3693-3701.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Klupp B. G., Mettenleiter T. C. Sequence and expression of the glycoprotein gH gene of pseudorabies virus. Virology. 1991 Jun;182(2):732–741. doi: 10.1016/0042-6822(91)90614-h. [DOI] [PubMed] [Google Scholar]
  29. Klupp B. G., Visser N., Mettenleiter T. C. Identification and characterization of pseudorabies virus glycoprotein H. J Virol. 1992 May;66(5):3048–3055. doi: 10.1128/jvi.66.5.3048-3055.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kopp A., Mettenleiter T. C. Stable rescue of a glycoprotein gII deletion mutant of pseudorabies virus by glycoprotein gI of bovine herpesvirus 1. J Virol. 1992 May;66(5):2754–2762. doi: 10.1128/jvi.66.5.2754-2762.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kornfeld R., Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. doi: 10.1146/annurev.bi.54.070185.003215. [DOI] [PubMed] [Google Scholar]
  32. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  33. MacLean C. A., Efstathiou S., Elliott M. L., Jamieson F. E., McGeoch D. J. Investigation of herpes simplex virus type 1 genes encoding multiply inserted membrane proteins. J Gen Virol. 1991 Apr;72(Pt 4):897–906. doi: 10.1099/0022-1317-72-4-897. [DOI] [PubMed] [Google Scholar]
  34. McGeoch D. J., Cook S. Molecular phylogeny of the alphaherpesvirinae subfamily and a proposed evolutionary timescale. J Mol Biol. 1994 Apr 22;238(1):9–22. doi: 10.1006/jmbi.1994.1264. [DOI] [PubMed] [Google Scholar]
  35. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P. The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol. 1988 Jul;69(Pt 7):1531–1574. doi: 10.1099/0022-1317-69-7-1531. [DOI] [PubMed] [Google Scholar]
  36. McLauchlan J., Gaffney D., Whitton J. L., Clements J. B. The consensus sequence YGTGTTYY located downstream from the AATAAA signal is required for efficient formation of mRNA 3' termini. Nucleic Acids Res. 1985 Feb 25;13(4):1347–1368. doi: 10.1093/nar/13.4.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. McMahan L., Schaffer P. A. The repressing and enhancing functions of the herpes simplex virus regulatory protein ICP27 map to C-terminal regions and are required to modulate viral gene expression very early in infection. J Virol. 1990 Jul;64(7):3471–3485. doi: 10.1128/jvi.64.7.3471-3485.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mettenleiter T. C. Pseudorabies (Aujeszky's disease) virus: state of the art. August 1993. Acta Vet Hung. 1994;42(2-3):153–177. [PubMed] [Google Scholar]
  39. Mettenleiter T. C., Rauh I. A glycoprotein gX-beta-galactosidase fusion gene as insertional marker for rapid identification of pseudorabies virus mutants. J Virol Methods. 1990 Oct;30(1):55–65. doi: 10.1016/0166-0934(90)90043-f. [DOI] [PubMed] [Google Scholar]
  40. Mizusawa S., Nishimura S., Seela F. Improvement of the dideoxy chain termination method of DNA sequencing by use of deoxy-7-deazaguanosine triphosphate in place of dGTP. Nucleic Acids Res. 1986 Feb 11;14(3):1319–1324. doi: 10.1093/nar/14.3.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Moyal M., Berkowitz C., Rösen-Wolff A., Darai G., Becker Y. Mutations in the UL53 gene of HSV-1 abolish virus neurovirulence to mice by the intracerebral route of infection. Virus Res. 1992 Nov;26(2):99–112. doi: 10.1016/0168-1702(92)90150-8. [DOI] [PubMed] [Google Scholar]
  42. Perera L. P., Kaushal S., Kinchington P. R., Mosca J. D., Hayward G. S., Straus S. E. Varicella-zoster virus open reading frame 4 encodes a transcriptional activator that is functionally distinct from that of herpes simplex virus homology ICP27. J Virol. 1994 Apr;68(4):2468–2477. doi: 10.1128/jvi.68.4.2468-2477.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Preston V. G., Fisher F. B. Identification of the herpes simplex virus type 1 gene encoding the dUTPase. Virology. 1984 Oct 15;138(1):58–68. doi: 10.1016/0042-6822(84)90147-8. [DOI] [PubMed] [Google Scholar]
  44. Ren D., Lee L. F., Coussens P. M. Identification and characterization of Marek's disease virus genes homologous to ICP27 and glycoprotein K of herpes simplex virus-1. Virology. 1994 Oct;204(1):242–250. doi: 10.1006/viro.1994.1528. [DOI] [PubMed] [Google Scholar]
  45. Rice S. A., Su L. S., Knipe D. M. Herpes simplex virus alpha protein ICP27 possesses separable positive and negative regulatory activities. J Virol. 1989 Aug;63(8):3399–3407. doi: 10.1128/jvi.63.8.3399-3407.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Roizmann B., Desrosiers R. C., Fleckenstein B., Lopez C., Minson A. C., Studdert M. J. The family Herpesviridae: an update. The Herpesvirus Study Group of the International Committee on Taxonomy of Viruses. Arch Virol. 1992;123(3-4):425–449. doi: 10.1007/BF01317276. [DOI] [PubMed] [Google Scholar]
  47. Rösen-Wolff A., Lamadé W., Berkowitz C., Becker Y., Darai G. Elimination of UL56 gene by insertion of LacZ cassette between nucleotide position 116030 to 121753 of the herpes simplex virus type 1 genome abrogates intraperitoneal pathogenicity in tree shrews and mice. Virus Res. 1991 Aug;20(3):205–221. doi: 10.1016/0168-1702(91)90076-8. [DOI] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. 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]
  51. Smith R. H., Zhao Y., O'Callaghan D. J. The equine herpesvirus 1 (EHV-1) UL3 gene, an ICP27 homolog, is necessary for full activation of gene expression directed by an EHV-1 late promoter. J Virol. 1993 Feb;67(2):1105–1109. doi: 10.1128/jvi.67.2.1105-1109.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Subramanian G., McClain D. S., Perez A., Fuller A. O. Swine testis cells contain functional heparan sulfate but are defective in entry of herpes simplex virus. J Virol. 1994 Sep;68(9):5667–5676. doi: 10.1128/jvi.68.9.5667-5676.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Sun Y., Brown S. M. The open reading frames 1, 2, 71, and 75 are nonessential for the replication of equine herpesvirus type 1 in vitro. Virology. 1994 Mar;199(2):448–452. doi: 10.1006/viro.1994.1143. [DOI] [PubMed] [Google Scholar]
  54. Telford E. A., Watson M. S., McBride K., Davison A. J. The DNA sequence of equine herpesvirus-1. Virology. 1992 Jul;189(1):304–316. doi: 10.1016/0042-6822(92)90706-u. [DOI] [PubMed] [Google Scholar]
  55. Vaughan P. J., Thibault K. J., Hardwicke M. A., Sandri-Goldin R. M. The herpes simplex virus immediate early protein ICP27 encodes a potential metal binding domain and binds zinc in vitro. Virology. 1992 Jul;189(1):377–384. doi: 10.1016/0042-6822(92)90720-a. [DOI] [PubMed] [Google Scholar]
  56. Yalamanchili R. R., Raengsakulrach B., O'Callaghan D. J. Equine herpesvirus 1 sequence near the left terminus codes for two open reading frames. Virus Res. 1991 Mar;18(2-3):109–116. doi: 10.1016/0168-1702(91)90012-k. [DOI] [PubMed] [Google Scholar]
  57. Zhao Y., Holden V. R., Harty R. N., O'Callaghan D. J. Identification and transcriptional analyses of the UL3 and UL4 genes of equine herpesvirus 1, homologs of the ICP27 and glycoprotein K genes of herpes simplex virus. J Virol. 1992 Sep;66(9):5363–5372. doi: 10.1128/jvi.66.9.5363-5372.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. doi: 10.1093/nar/14.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]

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