Analysis of the Bovine Herpesvirus Type 1 Thymidine Kinase (TK) Gene from Wild-type Virus and TK-deficient Mutants Free

Abstract

SUMMARY

Five thymidine kinase (TK)-deficient mutants (B1 to B5) of bovine herpesvirus type 1 (BHV-1) were isolated by selection for resistance to the nucleoside analogue bromovinyldeoxyuridine. The genetic lesion in mutant B1 was localized in a 2·7 kb I-I subfragment (fTK2.7) which maps between 0·456 and 0·475 within the III A fragment of the BHV-1 genome. The genes from wild-type and the TK mutants B1 to B5 were cloned and sequenced using eight unique synthetic primers designed from a published sequence. The BHV-1 gene sequence for the strain 6660 contained some differences compared with that published previously for strain LA. Alignment of the predicted amino acid sequence of the BHV-1 TK polypeptide with different herpesvirus TKs revealed five strongly conserved regions and also identified putative functional relationships with other enzymes. Several interesting features were apparent in the gene sequences from the TK mutants. The TK mutant B1 was a typical frameshift and chain termination mutant due to the deletion of a single base. The gene sequence of mutant B2 revealed the deletion of three bases resulting in the loss of valine at amino acid residue 174 of the TK polypeptide. The genes of mutants B3 to B5 contained an identical change of a single base addition resulting in frameshift and premature chain termination. In contrast to wild-type BHV-1, the TK-defective mutants were incapable of adsorbing TK-neutralizing antibodies from serum.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-70-4-901
1989-04-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/70/4/JV0700040901.html?itemId=/content/journal/jgv/10.1099/0022-1317-70-4-901&mimeType=html&fmt=ahah

References

  1. Babr R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Senguin C., Tuffnell P. S., Barrell B. G. 1984; DNA sequence and expression of the B958 Epstein—Barr virus genome. Nature, London 310:207–211
    [Google Scholar]
  2. Bankier A. T., Barrels B. G. 1983; Shotgun DNA sequencing. In Techniques in Life Seiences (Biochemistry)1–34 Flavell R. A. Amsterdam: Elsevier;
    [Google Scholar]
  3. Bello L. J., Whitbeck J. C., Lawrence W. C. 1987; Map location of the thymidine kinase gene of bovine herpesvirus 1. Journal of Virology 61:4023–4025
    [Google Scholar]
  4. Boyle D. B., Coupar E. H., Gibbs A. J., Seigman L. J., Both G. W. 1987; Fowlpox virus thymidine kinase: nucleotide sequences and relationship to other thymidine kinases. Virology 156:355–365
    [Google Scholar]
  5. Bradshaw H. D. JR, Deininger P. L. 1984; Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells. Molecular and Cellular Biology 4:2316–2320
    [Google Scholar]
  6. Coen D. M. 1986; General aspects of virus drug resistance with special reference to herpes simplex virus. Journal of Antimicrobial Chemotherapy 18: supplement B 1–10
    [Google Scholar]
  7. Darby G., Larder B. X., Inglis M. M. 1986; Evidence that the ‘active centre’ of herpes simplex virus thymidine kinase involves an interaction between three distinct regions of the polypeptide. Journal of General Virology 67:753–758
    [Google Scholar]
  8. Davison A. J., Scott J. E. 1986; The complete DNA sequence of varicella-zoster virus. Journal of General Virology 67:1759–1816
    [Google Scholar]
  9. Dentb L., Cesareni G., Cortese R. 1983; pEMBL: a new family of single stranded plasmids. Nucleic Acids Research 11:1645–1655
    [Google Scholar]
  10. Devereaux J., Haebereli P., Smithies O. 1984; A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Research 12:387–395
    [Google Scholar]
  11. Dhar R., Ellis R. W., Shih T. Y., Oroszlan S., Shapiro B., Maizel J., Lowy D., Scolnick E. 1982; Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus. Science 217:934–937
    [Google Scholar]
  12. Dubbs D. R., Kit S. 1964; Mutant strains of herpes simplex deficient in thymidine kinase-inducing ability. Virology 22:493–502
    [Google Scholar]
  13. Engels M., Giuliani C., Wild P., Beck T. M., Loefpe E., Wyler R. 1986/87; The genome of bovine herpesvirus 1 (BHV-I) strains exhibiting a neuropathogenic potential compared to known BHV-1 strains by restriction site mapping and cross-hydridization. Virus Research 6:57–73
    [Google Scholar]
  14. Field H. J. 1985; Resistance and latency. British Medical Bulletin 41:345–350
    [Google Scholar]
  15. Field H. J., Neden J. 1982; Isolation of bromovinyldeoxyuridirie-resistant strains of herpes simplex virus and successful chemotherapy of mice infected with one such strain by using acyclovir. Antiviral Research 2:243–254
    [Google Scholar]
  16. Field H. J., Owen L. 1988; The problem of virus drug resistance in antiviral drug development. In Antiviral Drug Derelopment: A Multidisciplinary Approach203–236 De Clercq E. New York & London: Plenum Press;
    [Google Scholar]
  17. Field H. J., Wildy P. 1978; The pathogenesis of thymidine kinase-deficient mutants of herpes simplex virus in mice. Journal of Hygiene 81:267–277
    [Google Scholar]
  18. Field H., Macmillan A., Derby G. 1981; The sensitivity of acyclovir-resistant mutants of herpes simplex virus to other antiviral drugs. Journal of Infectious Diseases 143:281–285
    [Google Scholar]
  19. Gay N. J., Walker J. E. 1983; Homology between human bladder carcinoma oncogene product and mitochondrial ATP-synthase. Nature, London 301:262–264
    [Google Scholar]
  20. Gentry G. A. 1985; Locating a nucleotide-binding site in the thymidine kinase of vaccinia virus and of herpes simplex virus by scoring triply aligned protein sequences. Proceedings of the National Academy of Sciences, U.S.A 82:6815–6819
    [Google Scholar]
  21. Gibbs E. P. J., Rweyemamu M. M. 1977; Bovine herpesviruses. Part I Veterinary Bulletin 47:317–343
    [Google Scholar]
  22. Graham F. L., Van Der Eb X. I. 1973; A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456–467
    [Google Scholar]
  23. Hammerschmidt W., Ludwig H., Ik Buhk H.-I. 1986; Short repeats cause heterogeneity at genomic terminus of bovine herpesvirus 1. Journal of Virology 58:43–49
    [Google Scholar]
  24. Haarr L., Flatmark T. 1987; Evidence that deletion of coding sequences in the 5′ end of the thymidine kinase gene of herpes simplex virus type 1 affects the stability of the gene products. Journal of General Virology 68:2817–2829
    [Google Scholar]
  25. Heil A., Muller G., Noda L., Pinder T., Schirmer H., Schirmer I., Von Zabern J. 1974; The amino-acid sequence of porcine adenylate kinase from skeletal muscle. European Joumol of Biochemistry 43:131–144
    [Google Scholar]
  26. Hruby D., Maki R. A., Miller D. B., Ball L. A. 1983; Fine structure analysis and nucleotide sequence of the vaccinia virus thymidine kinase gene. Proceedings of the National Academy of sciences, U.S.A 80:3411–3415
    [Google Scholar]
  27. Jamieson A. T., Gentry G. A., Subak-Sharpe J. H. 1974; Induction of both thymidine and deoxycytidine kinase activity by herpes viruses. Journal of General Virology 24:465–480
    [Google Scholar]
  28. Kit S. 1985; Thymidine kinase. Microbiological Sciences 2:369–375
    [Google Scholar]
  29. Kit M., Kit S. 1986; Thymidine kinase deletion mutants of bovine herpesvirus 1, vaccines against infectious bovine rhinotracheitis containing same and methods for the production and use of the same. European Patent Application Number 86115455.7
    [Google Scholar]
  30. Kit S., Qavi H. 1983; Thymidine kinase (TK) induction after infection of TK-deficient rabbit cell mutants with bovine herpesvirus type 1 (BHV-I): isolation of TK BHY-1 mutants. Virology 130:381–389
    [Google Scholar]
  31. Kit S., Sheppard M., Ichimura H., Nusinoff-Lehrman S., Elus M. N., Fyfe I. A., Otsuka H. 1987; Nucleotide sequence changes in thymidine kinase gene of herpes simplex virus type 2 clones from an isolate of a patient treated with acyclovir. Antimicrobial Agents and Chemotherapy 31:1483–1490
    [Google Scholar]
  32. Klemperer H. G., Haynes G. R., Shedden W. I. H., Watson D. H. 1967; A virus-specific thymidine kinase in BHK21 cells infected with herpes simplex virus. Virology 31:120–128
    [Google Scholar]
  33. Kuby S. A., Palmieri R. H., Frischat A., Fischer A. H., Wu L. H., Maland L., Manship M. 1984; Studies on adenosine triphosphate transphosphorylases. Amino acid sequence of rabbit muscle ATP-AMP transphos- phorylase. Biochemistry 23:2393–2399
    [Google Scholar]
  34. Kwoh T. J., Engler J. A. 1984; The nucleotide sequence of the chicken thymidine kinase gene and the relationship of its predicted polypeptide to that of the vaccinia virus thymidine kinase. Nucleic Acids Research 12:3959–3971
    [Google Scholar]
  35. Larder B. A., Darby G. 1984; Virus drug resistance: mechanisms and consequences. Antiviral Research 4:1–42
    [Google Scholar]
  36. Lawrence W. C., D’urso R. C., Kundel C. A., Whitbeck J. C., Bello L. J. 1986; Map location of the gene for a 130,000-dalton glycoprotein of bovine herpesvirus 1. Journal of. Virology 60:405–415
    [Google Scholar]
  37. Lee L.-S., Cheng Y.-C. 1976; Human deoxythymidine kinase. 1. Purification and general properties of the cytoplasmic and mitochondrial isoenzyme derived from blast cells of acute myelocytic leukemia. Journal of Biological Chemistry 251:2600–2604
    [Google Scholar]
  38. Lewis J. A. 1986; Structure and expression of the Chinese hamster thymidine kinase gene. Molecular and Cellular Biology 6:1998–2010
    [Google Scholar]
  39. Lin P.-F., Lieberman H. B., Yeh D.-B., Xu T., Zhao S.-Y., Ruddle F. H. 1985; Molecular cloning and structural analyses of murine thymidine kinase genomic and cDNA sequences. Molecular and Cellular Biology 5:3149–3156
    [Google Scholar]
  40. Lipman D. J., Pearson W. R. 1985; Rapid and sensitive protein similarity searches. Science 227:1435–1441
    [Google Scholar]
  41. Liu Q., Summers W. C. 1988; Site-directed mutagenesis of a nucleotide-binding domain in HSV-1 thymidine kinase: effects on catalytic activity. Virology 163:638–642
    [Google Scholar]
  42. Ludwig H. 1983; Bovine herpesviruses. In The Herpesuirwes 2135–214 Roizman B. New York: Plenum Press;
    [Google Scholar]
  43. Maniatis T., Fritsch E. F., Sambrook J. 1982; Molecular Cloning. A Laboratory Manual New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  44. Martin J. L., Ellis M. N., Keller P. M., Biron K. K., Lehrman S. N., Barry D. W., Furman P. A. 1985; Plaque autoradiographic assay for the detection and quantitation of thymidine kinase-deficient and thymidine kinase-altered mutants of herpes simplex in clinical isolates. Antimicrobial Agents and Chemotherapy 28:181–187
    [Google Scholar]
  45. Mayfield J. E., Good P. J., Van Oort H. J., Campbell A. R., Reed D. E. 1983; Cloning and cleavage site mapping of DNA from bovine herpesvirus 1 (Cooper strain). Journal of Virology 47:259–264
    [Google Scholar]
  46. Messing J., Vieira J. 1982; A new pair of M1 3 vectors for selecting either DNA strand of double-digest restriction fragments. Gene 19:269–276
    [Google Scholar]
  47. Otsuka H., Kit S. 1984; Nucleotide sequence of the marmoset herpesvirus thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide. Virology 135:316–330
    [Google Scholar]
  48. Owen L. J., Field H. I. 1988; Genomic localization and sequence analysis of the putative bovine herpesvirus-1 DNA polymerase gene. Archives of Virology 98:27–38
    [Google Scholar]
  49. Pai E. F., Sachsenheimer W., Schirmer R. H., Schulz G. E. 1977; Substrate positions and induced-fit in crystalline adenylate kinase. Journal of Molecular Biology 114:37–45
    [Google Scholar]
  50. Parris D. S., Harrington J. E. 1982; Herpes simplex virus variants resistant to high concentrations of acyclovir exist in clinical isolates. Antimicrobial Agents and Chemotherapy 22:71–77
    [Google Scholar]
  51. Roi Zman B., Batterson W. 1985; Herpesviruses and their replication. In Virology497–526 Fields B. N. New York: Raven Press;
    [Google Scholar]
  52. Sachsenheimer W., Schulz G. E. 1977; Two conformations of crystalline adenylate kinase. Journal of Molecular Biology 114:23–36
    [Google Scholar]
  53. Sancar A., Stachelek C., Konigsberg W., Rupp W. D. 1980; Sequence of the recA gene and protein. Proceedings of the National Academy of Sciences, U.S.A 77:2611–2615
    [Google Scholar]
  54. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A 74:5463–5467
    [Google Scholar]
  55. Saraste M., Gay N. J., Fberle A., Runswich M. J., Walker J. E. 1981; The atp operon : nucleotide sequence of the genes for the α, β and ε subunits of Escherichia coli ATP synthase. Nucleic Acids Research 9:5287–5296
    [Google Scholar]
  56. Staden R. 1986; The current status and probability of our sequence handling software. Nucleic Acids Research 14:217–231
    [Google Scholar]
  57. Stow N. D., Wilkie N. M. 1976; An improved technique for obtaining enhanced infectivity with herpes simplex virus type 1 DNA. Journal of General Virology 33:447–458
    [Google Scholar]
  58. Stow N. D., Subak-Sharpe I. H., Wilkie N. M. 1976; Physical mapping of herpes simplex virus type 1 mutants by marker rescue. Journal of Virology 28:182–192
    [Google Scholar]
  59. Summers W. P., Wagner M., Summers W. C. 1975; Possible chain termination mutants in thymidine kinase gene of a mammalian virus, herpes simplex virus. Proceedings of the National Academy of Sciences, U.S.A 72:5081–5084
    [Google Scholar]
  60. Swain M. A., Galloway D. x. 1983; Nucleotide sequence of the herpes simplex type 2 thymidine kinase gene. Journal of Virology 46:1045–1050
    [Google Scholar]
  61. Tenser R. B., Jones J. C., Ressel S. J., Fralish F. A. 1983; Thymidine plaque autoradiography of thymidine kinase-positive and thymidine kinase-negative herpesviruses. Journal of Clinical Microbiology 17:122–127
    [Google Scholar]
  62. Wagner M. J., Sharp J. A., Summers W. C. 1981; Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1. Proceedings of the National Academy of Sciences, U.S.A 78:1441–1445
    [Google Scholar]
  63. Walker J. E., Saraste M., Runswick M. J., Gay N. J. 1982; Distantly related sequences in the α- and β-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO Journal 1:945–951
    [Google Scholar]
  64. Weinmaster G. A., Misra V., Mcguire R., Babiuk L. A., De Clercq E. 1982; Bovid herpesvirus type-1 (infectious boy ine rhinotracheitis virus)-induced thymidine kinase. Virology 118:191–201
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-70-4-901
Loading
/content/journal/jgv/10.1099/0022-1317-70-4-901
Loading

Data & Media loading...

Most cited Most Cited RSS feed