Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases (original) (raw)

Abstract

Several recombinant cowpox viruses were constructed and used to identify a viral gene that controls the production of hemorrhage in lesions caused by the Brighton Red strain of cowpox virus (CPV-BR). This gene is located in the KpnD fragment of CPV-BR DNA, between 31 and 32 kilobases from the end of the genome. This position corresponds well with that predicted from analyses of the DNA structures of spontaneously generated deletion mutants. The gene responsible for hemorrhage encodes a 38-kDa protein that is one of the most abundant early gene products. The 11-base-pair sequence GAAAATATATT present 84 base pairs upstream of its coding region is also present upstream of three other early genes of vaccinia virus; therefore, this sequence may be involved in the regulation of transcription. There is extensive similarity between the predicted amino acid sequence of the 38-kDa protein and the amino acid sequences of several plasma proteins that are inhibitors of various serine proteases involved in blood coagulation pathways. This suggests that the viral protein may possess a similar biological activity, which may enable it to effect hemorrhage by inhibiting one or more of the serine proteases involved in the host's normal processes of blood coagulation and wound containment.

7698

Images in this article

Selected References

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

  1. Archard L. C., Mackett M., Barnes D. E., Dumbell K. R. The genome structure of cowpox virus white pock variants. J Gen Virol. 1984 May;65(Pt 5):875–886. doi: 10.1099/0022-1317-65-5-875. [DOI] [PubMed] [Google Scholar]
  2. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cochran M. A., Puckett C., Moss B. In vitro mutagenesis of the promoter region for a vaccinia virus gene: evidence for tandem early and late regulatory signals. J Virol. 1985 Apr;54(1):30–37. doi: 10.1128/jvi.54.1.30-37.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DOWNIE A. W., HADDOCK D. W. A variant of cowpox virus. Lancet. 1952 May 24;1(6717):1049–1050. doi: 10.1016/s0140-6736(52)90698-3. [DOI] [PubMed] [Google Scholar]
  5. Dayhoff M. O., Barker W. C., Hunt L. T. Establishing homologies in protein sequences. Methods Enzymol. 1983;91:524–545. doi: 10.1016/s0076-6879(83)91049-2. [DOI] [PubMed] [Google Scholar]
  6. Dumbell K. R., Archard L. C. Comparison of white pock (h) mutants of monkeypox virus with parental monkeypox and with variola-like viruses isolated from animals. Nature. 1980 Jul 3;286(5768):29–32. doi: 10.1038/286029a0. [DOI] [PubMed] [Google Scholar]
  7. Earl P. L., Jones E. V., Moss B. Homology between DNA polymerases of poxviruses, herpesviruses, and adenoviruses: nucleotide sequence of the vaccinia virus DNA polymerase gene. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3659–3663. doi: 10.1073/pnas.83.11.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Esposito J. J., Cabradilla C. D., Nakano J. H., Obijeski J. F. Intragenomic sequence transposition in monkeypox virus. Virology. 1981 Mar;109(2):231–243. doi: 10.1016/0042-6822(81)90495-5. [DOI] [PubMed] [Google Scholar]
  9. George D. G., Yeh L. S., Barker W. C. Unexpected relationships between bacteriophage lambda hypothetical proteins and bacteriophage T4 tail-fiber proteins. Biochem Biophys Res Commun. 1983 Sep 30;115(3):1061–1068. doi: 10.1016/s0006-291x(83)80043-6. [DOI] [PubMed] [Google Scholar]
  10. Griffith M. J., Noyes C. M., Church F. C. Reactive site peptide structural similarity between heparin cofactor II and antithrombin III. J Biol Chem. 1985 Feb 25;260(4):2218–2225. [PubMed] [Google Scholar]
  11. Hill R. E., Shaw P. H., Boyd P. A., Baumann H., Hastie N. D. Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions. Nature. 1984 Sep 13;311(5982):175–177. doi: 10.1038/311175a0. [DOI] [PubMed] [Google Scholar]
  12. Hunt L. T., Dayhoff M. O. A surprising new protein superfamily containing ovalbumin, antithrombin-III, and alpha 1-proteinase inhibitor. Biochem Biophys Res Commun. 1980 Jul 31;95(2):864–871. doi: 10.1016/0006-291x(80)90867-0. [DOI] [PubMed] [Google Scholar]
  13. Jackson R. J., Hunt T. Preparation and use of nuclease-treated rabbit reticulocyte lysates for the translation of eukaryotic messenger RNA. Methods Enzymol. 1983;96:50–74. doi: 10.1016/s0076-6879(83)96008-1. [DOI] [PubMed] [Google Scholar]
  14. Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
  15. Kurachi K., Chandra T., Degen S. J., White T. T., Marchioro T. L., Woo S. L., Davie E. W. Cloning and sequence of cDNA coding for alpha 1-antitrypsin. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6826–6830. doi: 10.1073/pnas.78.11.6826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Loebermann H., Tokuoka R., Deisenhofer J., Huber R. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J Mol Biol. 1984 Aug 15;177(3):531–557. [PubMed] [Google Scholar]
  17. Mackett M., Smith G. L., Moss B. Vaccinia virus: a selectable eukaryotic cloning and expression vector. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7415–7419. doi: 10.1073/pnas.79.23.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  19. Morii M., Travis J. Amino acid sequence at the reactive site of human alpha 1-antichymotrypsin. J Biol Chem. 1983 Nov 10;258(21):12749–12752. [PubMed] [Google Scholar]
  20. Moyer R. W., Graves R. L., Rothe C. T. The white pock (mu) mutants of rabbit poxvirus. III. Terminal DNA sequence duplication and transposition in rabbit poxvirus. Cell. 1980 Nov;22(2 Pt 2):545–553. doi: 10.1016/0092-8674(80)90364-5. [DOI] [PubMed] [Google Scholar]
  21. Patel D. D., Pickup D. J., Joklik W. K. Isolation of cowpox virus A-type inclusions and characterization of their major protein component. Virology. 1986 Mar;149(2):174–189. doi: 10.1016/0042-6822(86)90119-4. [DOI] [PubMed] [Google Scholar]
  22. Pickup D. J., Ink B. S., Parsons B. L., Hu W., Joklik W. K. Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6817–6821. doi: 10.1073/pnas.81.21.6817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Plucienniczak A., Schroeder E., Zettlmeissl G., Streeck R. E. Nucleotide sequence of a cluster of early and late genes in a conserved segment of the vaccinia virus genome. Nucleic Acids Res. 1985 Feb 11;13(3):985–998. doi: 10.1093/nar/13.3.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ricciardi R. P., Miller J. S., Roberts B. E. Purification and mapping of specific mRNAs by hybridization-selection and cell-free translation. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4927–4931. doi: 10.1073/pnas.76.10.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. VAN TONGEREN H. A. E. Spontaneous mutation of cowpox-virus by means of egg-passage. Arch Gesamte Virusforsch. 1952;5(1):35–52. doi: 10.1007/BF01245138. [DOI] [PubMed] [Google Scholar]
  26. Venkatesan S., Baroudy B. M., Moss B. Distinctive nucleotide sequences adjacent to multiple initiation and termination sites of an early vaccinia virus gene. Cell. 1981 Sep;25(3):805–813. doi: 10.1016/0092-8674(81)90188-4. [DOI] [PubMed] [Google Scholar]