Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Aug;69(8):4633–4639. doi: 10.1128/jvi.69.8.4633-4639.1995

Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity.

A Alcamí 1, G L Smith 1
PMCID: PMC189264  PMID: 7609027

Abstract

Soluble receptors for gamma interferon (IFN-gamma) are secreted from cells infected by 17 orthopoxviruses, including vaccinia, cowpox, rabbitpox, buffalopox, elephantpox, and camelpox viruses, representing three species (vaccinia, cowpox, and campelpox viruses). The B8R open reading frame of vaccinia virus strain Western Reserve, which has sequence similarity to the extracellular binding domain of cellular IFN-gamma receptors (IFN-gamma Rs), is shown to encode an IFN-gamma binding activity by expression in recombinant baculovirus. The soluble virus IFN-gamma Rs bind IFN-gamma and, by preventing its interaction with the cellular receptor, interfere with the antiviral effects induced by this cytokine. Interestingly, in contrast to cellular IFN-gamma Rs, which are highly species specific, the vaccinia, cowpox, and camelpox virus IFN-gamma Rs bind and inhibit the biological activity of human, bovine, and rat IFN-gamma but not mouse IFN-gamma. This unique broad species specificity of the IFN-gamma R would aid virus replication in different species and suggests that vaccinia, cowpox, and camelpox viruses may have evolved in several species, possibly including humans but excluding mice. Last, the conservation of an IFN-gamma R in orthopoxviruses emphasizes the importance of IFN-gamma in defense against poxvirus infections.

Full Text

The Full Text of this article is available as a PDF (563.5 KB).

Selected References

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

  1. Aguado B., Selmes I. P., Smith G. L. Nucleotide sequence of 21.8 kbp of variola major virus strain Harvey and comparison with vaccinia virus. J Gen Virol. 1992 Nov;73(Pt 11):2887–2902. doi: 10.1099/0022-1317-73-11-2887. [DOI] [PubMed] [Google Scholar]
  2. Alcamí A., Smith G. L. A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel mechanism of virus modulation of the host response to infection. Cell. 1992 Oct 2;71(1):153–167. doi: 10.1016/0092-8674(92)90274-g. [DOI] [PubMed] [Google Scholar]
  3. Alcamí A., Smith G. L. Comment on the paper by Shchelkunov et al. (1993) FEBS Letters 319, 80-83. Two genes encoding poxvirus cytokine receptors are disrupted or deleted in variola virus. FEBS Lett. 1993 Nov 29;335(1):136–138. doi: 10.1016/0014-5793(93)80455-4. [DOI] [PubMed] [Google Scholar]
  4. Beattie E., Tartaglia J., Paoletti E. Vaccinia virus-encoded eIF-2 alpha homolog abrogates the antiviral effect of interferon. Virology. 1991 Jul;183(1):419–422. doi: 10.1016/0042-6822(91)90158-8. [DOI] [PubMed] [Google Scholar]
  5. Buller R. M., Palumbo G. J. Poxvirus pathogenesis. Microbiol Rev. 1991 Mar;55(1):80–122. doi: 10.1128/mr.55.1.80-122.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang H. W., Watson J. C., Jacobs B. L. The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4825–4829. doi: 10.1073/pnas.89.11.4825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Czarniecki C. W., Hamilton E. B., Fennie C. W., Wolf R. L. In vitro biological activities of Escherichia coli-derived bovine interferons-alpha, -beta, and -gamma. J Interferon Res. 1986 Feb;6(1):29–37. doi: 10.1089/jir.1986.6.29. [DOI] [PubMed] [Google Scholar]
  8. Davies M. V., Elroy-Stein O., Jagus R., Moss B., Kaufman R. J. The vaccinia virus K3L gene product potentiates translation by inhibiting double-stranded-RNA-activated protein kinase and phosphorylation of the alpha subunit of eukaryotic initiation factor 2. J Virol. 1992 Apr;66(4):1943–1950. doi: 10.1128/jvi.66.4.1943-1950.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dijkema R., van der Meide P. H., Pouwels P. H., Caspers M., Dubbeld M., Schellekens H. Cloning and expression of the chromosomal immune interferon gene of the rat. EMBO J. 1985 Mar;4(3):761–767. doi: 10.1002/j.1460-2075.1985.tb03694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dower S. K., Kronheim S. R., March C. J., Conlon P. J., Hopp T. P., Gillis S., Urdal D. L. Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. J Exp Med. 1985 Aug 1;162(2):501–515. doi: 10.1084/jem.162.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Farrar M. A., Schreiber R. D. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol. 1993;11:571–611. doi: 10.1146/annurev.iy.11.040193.003035. [DOI] [PubMed] [Google Scholar]
  12. Goebel S. J., Johnson G. P., Perkus M. E., Davis S. W., Winslow J. P., Paoletti E. The complete DNA sequence of vaccinia virus. Virology. 1990 Nov;179(1):247-66, 517-63. doi: 10.1016/0042-6822(90)90294-2. [DOI] [PubMed] [Google Scholar]
  13. Howard S. T., Chan Y. S., Smith G. L. Vaccinia virus homologues of the Shope fibroma virus inverted terminal repeat proteins and a discontinuous ORF related to the tumor necrosis factor receptor family. Virology. 1991 Feb;180(2):633–647. doi: 10.1016/0042-6822(91)90077-o. [DOI] [PubMed] [Google Scholar]
  14. Hu F. Q., Smith C. A., Pickup D. J. Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor. Virology. 1994 Oct;204(1):343–356. doi: 10.1006/viro.1994.1539. [DOI] [PubMed] [Google Scholar]
  15. Huang S., Hendriks W., Althage A., Hemmi S., Bluethmann H., Kamijo R., Vilcek J., Zinkernagel R. M., Aguet M. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742–1745. doi: 10.1126/science.8456301. [DOI] [PubMed] [Google Scholar]
  16. JONKERS A. H., SHOPE R. E., AITKEN T. H., SPENCE L. COCAL VIRUS, A NEW AGENT IN TRINIDAD RELATED TO VESICULAR STOMATITIS VIRUS, TYPE INDIANA. Am J Vet Res. 1964 Jan;25:236–242. [PubMed] [Google Scholar]
  17. Karupiah G., Xie Q. W., Buller R. M., Nathan C., Duarte C., MacMicking J. D. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science. 1993 Sep 10;261(5127):1445–1448. doi: 10.1126/science.7690156. [DOI] [PubMed] [Google Scholar]
  18. Kohonen-Corish M. R., King N. J., Woodhams C. E., Ramshaw I. A. Immunodeficient mice recover from infection with vaccinia virus expressing interferon-gamma. Eur J Immunol. 1990 Jan;20(1):157–161. doi: 10.1002/eji.1830200123. [DOI] [PubMed] [Google Scholar]
  19. Marennikova S. S., Ladnyj I. D., Ogorodinikova Z. I., Shelukhina E. M., Maltseva N. N. Identification and study of a poxvirus isolated from wild rodents in Turkmenia. Arch Virol. 1978;56(1-2):7–14. doi: 10.1007/BF01317279. [DOI] [PubMed] [Google Scholar]
  20. Massung R. F., Esposito J. J., Liu L. I., Qi J., Utterback T. R., Knight J. C., Aubin L., Yuran T. E., Parsons J. M., Loparev V. N. Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature. 1993 Dec 23;366(6457):748–751. doi: 10.1038/366748a0. [DOI] [PubMed] [Google Scholar]
  21. Massung R. F., Jayarama V., Moyer R. W. DNA sequence analysis of conserved and unique regions of swinepox virus: identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue. Virology. 1993 Dec;197(2):511–528. doi: 10.1006/viro.1993.1625. [DOI] [PubMed] [Google Scholar]
  22. Massung R. F., Liu L. I., Qi J., Knight J. C., Yuran T. E., Kerlavage A. R., Parsons J. M., Venter J. C., Esposito J. J. Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. Virology. 1994 Jun;201(2):215–240. doi: 10.1006/viro.1994.1288. [DOI] [PubMed] [Google Scholar]
  23. Matsuura Y., Possee R. D., Overton H. A., Bishop D. H. Baculovirus expression vectors: the requirements for high level expression of proteins, including glycoproteins. J Gen Virol. 1987 May;68(Pt 5):1233–1250. doi: 10.1099/0022-1317-68-5-1233. [DOI] [PubMed] [Google Scholar]
  24. Melková Z., Esteban M. Interferon-gamma severely inhibits DNA synthesis of vaccinia virus in a macrophage cell line. Virology. 1994 Feb;198(2):731–735. doi: 10.1006/viro.1994.1087. [DOI] [PubMed] [Google Scholar]
  25. Mossman K., Upton C., McFadden G. The myxoma virus-soluble interferon-gamma receptor homolog, M-T7, inhibits interferon-gamma in a species-specific manner. J Biol Chem. 1995 Feb 17;270(7):3031–3038. doi: 10.1074/jbc.270.7.3031. [DOI] [PubMed] [Google Scholar]
  26. Novick D., Engelmann H., Wallach D., Rubinstein M. Soluble cytokine receptors are present in normal human urine. J Exp Med. 1989 Oct 1;170(4):1409–1414. doi: 10.1084/jem.170.4.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  28. Shchelkunov S. N., Blinov V. M., Sandakhchiev L. S. Genes of variola and vaccinia viruses necessary to overcome the host protective mechanisms. FEBS Lett. 1993 Mar 15;319(1-2):80–83. doi: 10.1016/0014-5793(93)80041-r. [DOI] [PubMed] [Google Scholar]
  29. Smith C. A., Davis T., Wignall J. M., Din W. S., Farrah T., Upton C., McFadden G., Goodwin R. G. T2 open reading frame from the Shope fibroma virus encodes a soluble form of the TNF receptor. Biochem Biophys Res Commun. 1991 Apr 15;176(1):335–342. doi: 10.1016/0006-291x(91)90929-2. [DOI] [PubMed] [Google Scholar]
  30. Smith G. L. Vaccinia virus glycoproteins and immune evasion. The sixteenth Fleming Lecture. J Gen Virol. 1993 Sep;74(Pt 9):1725–1740. doi: 10.1099/0022-1317-74-9-1725. [DOI] [PubMed] [Google Scholar]
  31. Spriggs M. K., Hruby D. E., Maliszewski C. R., Pickup D. J., Sims J. E., Buller R. M., VanSlyke J. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell. 1992 Oct 2;71(1):145–152. doi: 10.1016/0092-8674(92)90273-f. [DOI] [PubMed] [Google Scholar]
  32. Upton C., Macen J. L., Schreiber M., McFadden G. Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence. Virology. 1991 Sep;184(1):370–382. doi: 10.1016/0042-6822(91)90853-4. [DOI] [PubMed] [Google Scholar]
  33. Upton C., Mossman K., McFadden G. Encoding of a homolog of the IFN-gamma receptor by myxoma virus. Science. 1992 Nov 20;258(5086):1369–1372. doi: 10.1126/science.1455233. [DOI] [PubMed] [Google Scholar]
  34. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  35. Wold W. S., Gooding L. R. Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology. 1991 Sep;184(1):1–8. doi: 10.1016/0042-6822(91)90815-s. [DOI] [PubMed] [Google Scholar]
  36. van der Meide P. H., Dubbeld M., Vijverberg K., Kos T., Schellekens H. The purification and characterization of rat gamma interferon by use of two monoclonal antibodies. J Gen Virol. 1986 Jun;67(Pt 6):1059–1071. doi: 10.1099/0022-1317-67-6-1059. [DOI] [PubMed] [Google Scholar]

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

RESOURCES