Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Feb;70(2):1213–1217. doi: 10.1128/jvi.70.2.1213-1217.1996

Replication properties of dUTPase-deficient mutants of caprine and ovine lentiviruses.

P Turelli 1, G Pétursson 1, F Guiguen 1, J F Mornex 1, R Vigne 1, G Quérat 1
PMCID: PMC189930  PMID: 8551582

Abstract

The virion-associated dUTPase activities of caprine arthritis-encephalitis virus (CAEV) and visna virus were determined by using an assay which measure the actual ability of the dUTPase to prevent the dUTP misincorporations into cDNA during reverse transcription. We showed that the CAEV molecular clone from the Cork isolate was dUTPase defective as a result of a single amino acid substitution. Using this point mutant and deletion mutants of CAEV as well as a deletion mutant of visna virus, we demonstrated that dUTPase-deficient viruses replicate similarly to wild-type viruses in dividing cells but show delayed replication in nondividing primary macrophages.

Full Text

The Full Text of this article is available as a PDF (230.1 KB).

Selected References

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

  1. Andrésson O. S., Elser J. E., Tobin G. J., Greenwood J. D., Gonda M. A., Georgsson G., Andrésdóttir V., Benediktsdóttir E., Carlsdóttir H. M., Mäntylä E. O. Nucleotide sequence and biological properties of a pathogenic proviral molecular clone of neurovirulent visna virus. Virology. 1993 Mar;193(1):89–105. doi: 10.1006/viro.1993.1106. [DOI] [PubMed] [Google Scholar]
  2. Bouhamdan M., Benichou S., Rey F., Navarro J. M., Agostini I., Spire B., Camonis J., Slupphaug G., Vigne R., Benarous R. Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme. J Virol. 1996 Feb;70(2):697–704. doi: 10.1128/jvi.70.2.697-704.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broyles S. S. Vaccinia virus encodes a functional dUTPase. Virology. 1993 Aug;195(2):863–865. doi: 10.1006/viro.1993.1446. [DOI] [PubMed] [Google Scholar]
  4. Caradonna S. J., Cheng Y. C. Induction of uracil-DNA glycosylase and dUTP nucleotidohydrolase activity in herpes simplex virus-infected human cells. J Biol Chem. 1981 Oct 10;256(19):9834–9837. [PubMed] [Google Scholar]
  5. Cork L. C., Hadlow W. J., Crawford T. B., Gorham J. R., Piper R. C. Infectious leukoencephalomyelitis of young goats. J Infect Dis. 1974 Feb;129(2):134–141. doi: 10.1093/infdis/129.2.134. [DOI] [PubMed] [Google Scholar]
  6. Crawford T. B., Adams D. S., Cheevers W. P., Cork L. C. Chronic arthritis in goats caused by a retrovirus. Science. 1980 Feb 29;207(4434):997–999. doi: 10.1126/science.6153243. [DOI] [PubMed] [Google Scholar]
  7. Doignon F., Biteau N., Aigle M., Crouzet M. The complete sequence of a 6794 bp segment located on the right arm of chromosome II of Saccharomyces cerevisiae. Finding of a putative dUTPase in a yeast. Yeast. 1993 Oct;9(10):1131–1137. doi: 10.1002/yea.320091014. [DOI] [PubMed] [Google Scholar]
  8. Elder J. H., Lerner D. L., Hasselkus-Light C. S., Fontenot D. J., Hunter E., Luciw P. A., Montelaro R. C., Phillips T. R. Distinct subsets of retroviruses encode dUTPase. J Virol. 1992 Mar;66(3):1791–1794. doi: 10.1128/jvi.66.3.1791-1794.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Elder J. H., Schnölzer M., Hasselkus-Light C. S., Henson M., Lerner D. A., Phillips T. R., Wagaman P. C., Kent S. B. Identification of proteolytic processing sites within the Gag and Pol polyproteins of feline immunodeficiency virus. J Virol. 1993 Apr;67(4):1869–1876. doi: 10.1128/jvi.67.4.1869-1876.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gendelman H. E., Narayan O., Kennedy-Stoskopf S., Kennedy P. G., Ghotbi Z., Clements J. E., Stanley J., Pezeshkpour G. Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol. 1986 Apr;58(1):67–74. doi: 10.1128/jvi.58.1.67-74.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hokari S., Hasegawa M., Sakagishi Y., Kikuchi G. Deoxyuridine triphosphate nucleotidohydrolase activity and its correlation with multiplication of erythroid cells in rat spleen. Biochem Int. 1987 May;14(5):851–857. [PubMed] [Google Scholar]
  12. Hokari S., Sakagishi Y., Tsukada K. Enhanced activity of deoxyuridine 5'-triphosphatase in regenerating rat liver. Biochem Biophys Res Commun. 1982 Sep 16;108(1):95–101. doi: 10.1016/0006-291x(82)91836-8. [DOI] [PubMed] [Google Scholar]
  13. Lichtenstein D. L., Rushlow K. E., Cook R. F., Raabe M. L., Swardson C. J., Kociba G. J., Issel C. J., Montelaro R. C. Replication in vitro and in vivo of an equine infectious anemia virus mutant deficient in dUTPase activity. J Virol. 1995 May;69(5):2881–2888. doi: 10.1128/jvi.69.5.2881-2888.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McClure M. A., Johnson M. S., Doolittle R. F. Relocation of a protease-like gene segment between two retroviruses. Proc Natl Acad Sci U S A. 1987 May;84(9):2693–2697. doi: 10.1073/pnas.84.9.2693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McGeoch D. J. Protein sequence comparisons show that the 'pseudoproteases' encoded by poxviruses and certain retroviruses belong to the deoxyuridine triphosphatase family. Nucleic Acids Res. 1990 Jul 25;18(14):4105–4110. doi: 10.1093/nar/18.14.4105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Narayan O., Kennedy-Stoskopf S., Sheffer D., Griffin D. E., Clements J. E. Activation of caprine arthritis-encephalitis virus expression during maturation of monocytes to macrophages. Infect Immun. 1983 Jul;41(1):67–73. doi: 10.1128/iai.41.1.67-73.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Narayan O., Wolinsky J. S., Clements J. E., Strandberg J. D., Griffin D. E., Cork L. C. Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats. J Gen Virol. 1982 Apr;59(Pt 2):345–356. doi: 10.1099/0022-1317-59-2-345. [DOI] [PubMed] [Google Scholar]
  18. Pardo E. G., Gutiérrez C. Cell cycle- and differentiation stage-dependent variation of dUTPase activity in higher plant cells. Exp Cell Res. 1990 Jan;186(1):90–98. doi: 10.1016/0014-4827(90)90214-u. [DOI] [PubMed] [Google Scholar]
  19. Pu W. T., Struhl K. Uracil interference, a rapid and general method for defining protein-DNA interactions involving the 5-methyl group of thymines: the GCN4-DNA complex. Nucleic Acids Res. 1992 Feb 25;20(4):771–775. doi: 10.1093/nar/20.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pyles R. B., Thompson R. L. Mutations in accessory DNA replicating functions alter the relative mutation frequency of herpes simplex virus type 1 strains in cultured murine cells. J Virol. 1994 Jul;68(7):4514–4524. doi: 10.1128/jvi.68.7.4514-4524.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pyper J. M., Clements J. E., Gonda M. A., Narayan O. Sequence homology between cloned caprine arthritis encephalitis virus and visna virus, two neurotropic lentiviruses. J Virol. 1986 May;58(2):665–670. doi: 10.1128/jvi.58.2.665-670.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Querat G., Audoly G., Sonigo P., Vigne R. Nucleotide sequence analysis of SA-OMVV, a visna-related ovine lentivirus: phylogenetic history of lentiviruses. Virology. 1990 Apr;175(2):434–447. doi: 10.1016/0042-6822(90)90428-t. [DOI] [PubMed] [Google Scholar]
  23. Quérat G., Barban V., Sauze N., Vigne R., Payne A., York D., De Villiers E. M., Verwoerd D. W. Characteristics of a novel lentivirus derived from South African sheep with pulmonary adenocarcinoma (jaagsiekte). Virology. 1987 May;158(1):158–167. doi: 10.1016/0042-6822(87)90249-2. [DOI] [PubMed] [Google Scholar]
  24. SIGURDSSON B., PALSSON P. A. Visna of sheep; a slow, demyelinating infection. Br J Exp Pathol. 1958 Oct;39(5):519–528. [PMC free article] [PubMed] [Google Scholar]
  25. Saltarelli M., Querat G., Konings D. A., Vigne R., Clements J. E. Nucleotide sequence and transcriptional analysis of molecular clones of CAEV which generate infectious virus. Virology. 1990 Nov;179(1):347–364. doi: 10.1016/0042-6822(90)90303-9. [DOI] [PubMed] [Google Scholar]
  26. Sargan D. R., Bennet I. D., Cousens C., Roy D. J., Blacklaws B. A., Dalziel R. G., Watt N. J., McConnell I. Nucleotide sequence of EV1, a British isolate of maedi-visna virus. J Gen Virol. 1991 Aug;72(Pt 8):1893–1903. doi: 10.1099/0022-1317-72-8-1893. [DOI] [PubMed] [Google Scholar]
  27. Sonigo P., Alizon M., Staskus K., Klatzmann D., Cole S., Danos O., Retzel E., Tiollais P., Haase A., Wain-Hobson S. Nucleotide sequence of the visna lentivirus: relationship to the AIDS virus. Cell. 1985 Aug;42(1):369–382. doi: 10.1016/s0092-8674(85)80132-x. [DOI] [PubMed] [Google Scholar]
  28. Spector R., Boose B. Development and regional distribution of deoxyuridine 5'-triphosphatase in rabbit brain. J Neurochem. 1983 Oct;41(4):1192–1195. doi: 10.1111/j.1471-4159.1983.tb09073.x. [DOI] [PubMed] [Google Scholar]
  29. Spire B., Sire J., Zachar V., Rey F., Barré-Sinoussi F., Galibert F., Hampe A., Chermann J. C. Nucleotide sequence of HIV1-NDK: a highly cytopathic strain of the human immunodeficiency virus. Gene. 1989 Sep 30;81(2):275–284. doi: 10.1016/0378-1119(89)90188-1. [DOI] [PubMed] [Google Scholar]
  30. Strahler J. R., Zhu X. X., Hora N., Wang Y. K., Andrews P. C., Roseman N. A., Neel J. V., Turka L., Hanash S. M. Maturation stage and proliferation-dependent expression of dUTPase in human T cells. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):4991–4995. doi: 10.1073/pnas.90.11.4991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Talbott R. L., Sparger E. E., Lovelace K. M., Fitch W. M., Pedersen N. C., Luciw P. A., Elder J. H. Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5743–5747. doi: 10.1073/pnas.86.15.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Terai C., Carson D. A. Pyrimidine nucleotide and nucleic acid synthesis in human monocytes and macrophages. Exp Cell Res. 1991 Apr;193(2):375–381. doi: 10.1016/0014-4827(91)90110-g. [DOI] [PubMed] [Google Scholar]
  33. Threadgill D. S., Steagall W. K., Flaherty M. T., Fuller F. J., Perry S. T., Rushlow K. E., Le Grice S. F., Payne S. L. Characterization of equine infectious anemia virus dUTPase: growth properties of a dUTPase-deficient mutant. J Virol. 1993 May;67(5):2592–2600. doi: 10.1128/jvi.67.5.2592-2600.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Verri A., Mazzarello P., Biamonti G., Spadari S., Focher F. The specific binding of nuclear protein(s) to the cAMP responsive element (CRE) sequence (TGACGTCA) is reduced by the misincorporation of U and increased by the deamination of C. Nucleic Acids Res. 1990 Oct 11;18(19):5775–5780. doi: 10.1093/nar/18.19.5775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Vertessy B. G., Zeppezauer M. Identification of tyrosine as an active site residue involved in the catalytic mechanism of Escherichia coli dUTPase. Biochem Soc Trans. 1994 May;22(2):233S–233S. doi: 10.1042/bst022233s. [DOI] [PubMed] [Google Scholar]
  36. Wagaman P. C., Hasselkus-Light C. S., Henson M., Lerner D. L., Phillips T. R., Elder J. H. Molecular cloning and characterization of deoxyuridine triphosphatase from feline immunodeficiency virus (FIV). Virology. 1993 Oct;196(2):451–457. doi: 10.1006/viro.1993.1501. [DOI] [PubMed] [Google Scholar]
  37. Wain-Hobson S., Sonigo P., Guyader M., Gazit A., Henry M. Erratic G-->A hypermutation within a complete caprine arthritis-encephalitis virus (CAEV) provirus. Virology. 1995 Jun 1;209(2):297–303. doi: 10.1006/viro.1995.1261. [DOI] [PubMed] [Google Scholar]
  38. Williams M. V., Cheng Y. Human deoxyuridine triphosphate nucleotidohydrolase. Purification and characterization of the deoxyuridine triphosphate nucleotidohydrolase from acute lymphocytic leukemia. J Biol Chem. 1979 Apr 25;254(8):2897–2901. [PubMed] [Google Scholar]
  39. Williams M. V., Parris D. S. Characterization of a herpes simplex virus type 2 deoxyuridine triphosphate nucleotidohydrolase and mapping of a gene conferring type specificity for the enzyme. Virology. 1987 Feb;156(2):282–292. doi: 10.1016/0042-6822(87)90408-9. [DOI] [PubMed] [Google Scholar]

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

RESOURCES