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. 1992 Dec;66(12):7073–7079. doi: 10.1128/jvi.66.12.7073-7079.1992

Serial backcross analysis of genetic resistance to mousepox, using marker loci for Rmp-2 and Rmp-3.

D G Brownstein 1, P N Bhatt 1, L Gras 1, T Budris 1
PMCID: PMC240377  PMID: 1433507

Abstract

At least three genes from C57BL/6 mice that mediate dominant resistance to lethal mousepox were isolated and transferred onto a susceptible DBA/2 background. Three [(C57BL/6 x DBA/2)F1 x DBA/2] male mice that survived infection were selected as founders on the basis of different complements of marker loci for two resistance genes, Rmp-2r (Hc1) and Rmp-3r (H-2Db). They were crossed with DBA/2 mice, male progeny were infected with ectromelia virus, and the cycle was repeated with surviving male progeny through seven backcross generations. Two founders carried a marker locus for Rmp-2r or Rmp-3r, and the third carried neither marker locus. Resistance pedigrees were analyzed for passage of marker loci. From the three founders, resistance was passaged through multiple generations, producing backcross lines with intermediate-male-resistance phenotypes (20% resistant). Females of backcross lines with intermediate male resistance had high resistance (> 50%). High-resistance backcross lines (40% male resistance) also developed from the founders that carried marker loci for Rmp-2r and Rmp-3r, and marker loci were passaged through all generations of high resistance but not intermediate-resistance lines. About one-third of all resistant mice in high-resistance lines sired by mice that carried marker loci for Rmp-2r and Rmp-3r did not carry the respective marker locus. In lines that carried Rmp-2r, this was apparently not the result of recombination between Rmp-2r and Hc1, because Rmp-2 was not in the predicted location on chromosome 2 and because mice that did not inherit Hc1 transmitted significantly less male resistance than Hc1-positive mice, although female resistance remained high. These results confirmed that C57BL/6 mice have redundant resistance mechanisms, two of which are controlled at least in part by Rmp-2r and Rmp-3r, and provided evidence for a fourth resistance gene, herein presumptively named Rmp-4, which protects females more than males and which may be epistatic to Rmp-2.

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Selected References

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  1. BRIODY B. A., HAUSCHKA T. S., MIRAND E. A. The role of genotype in resistance to an epizootic of mouse pox (ectromelia). Am J Hyg. 1956 Jan;63(1):59–68. doi: 10.1093/oxfordjournals.aje.a119792. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bhatt P. N., Jacoby R. O., Gras L. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. IV. Studies with the Moscow strain. Arch Virol. 1988;100(3-4):221–230. doi: 10.1007/BF01487685. [DOI] [PubMed] [Google Scholar]
  4. Boyle J. F., Weismiller D. G., Holmes K. V. Genetic resistance to mouse hepatitis virus correlates with absence of virus-binding activity on target tissues. J Virol. 1987 Jan;61(1):185–189. doi: 10.1128/jvi.61.1.185-189.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brownstein D. G., Bhatt P. N., Gras L., Jacoby R. O. Chromosomal locations and gonadal dependence of genes that mediate resistance to ectromelia (mousepox) virus-induced mortality. J Virol. 1991 Apr;65(4):1946–1951. doi: 10.1128/jvi.65.4.1946-1951.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brownstein D., Bhatt P. N., Jacoby R. O. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. V. Genetics of resistance to the Moscow strain. Arch Virol. 1989;107(1-2):35–41. doi: 10.1007/BF01313876. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Eidinger D., Garrett T. J. Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation. J Exp Med. 1972 Nov 1;136(5):1098–1116. doi: 10.1084/jem.136.5.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Esposito J. J., Knight J. C. Orthopoxvirus DNA: a comparison of restriction profiles and maps. Virology. 1985 May;143(1):230–251. doi: 10.1016/0042-6822(85)90111-4. [DOI] [PubMed] [Google Scholar]
  10. Esposito J. J., Obijeski J. F., Nakano J. H. Orthopoxvirus DNA: strain differentiation by electrophoresis of restriction endonuclease fragmented virion DNA. Virology. 1978 Aug;89(1):53–66. doi: 10.1016/0042-6822(78)90039-9. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Gröschel D., Koprowski H. Development of a virus-resistant inbred mouse strain for the study of innate resistance to Arbo B viruses. Arch Gesamte Virusforsch. 1965;17(3):379–391. doi: 10.1007/BF01241192. [DOI] [PubMed] [Google Scholar]
  13. Horisberger M. A., Staeheli P., Haller O. Interferon induces a unique protein in mouse cells bearing a gene for resistance to influenza virus. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1910–1914. doi: 10.1073/pnas.80.7.1910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacoby R. O., Bhatt P. N., Brownstein D. G. Evidence that NK cells and interferon are required for genetic resistance to lethal infection with ectromelia virus. Arch Virol. 1989;108(1-2):49–58. doi: 10.1007/BF01313742. [DOI] [PubMed] [Google Scholar]
  15. Jacoby R. O., Bhatt P. N., Johnson E. A., Paturzo F. X. Pathogenesis of vaccinia (IHD-T) virus infection in BALB/cAnN mice. Lab Anim Sci. 1983 Oct;33(5):435–441. [PubMed] [Google Scholar]
  16. Jacoby R. O., Bhatt P. N. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. II. Pathogenesis. Lab Anim Sci. 1987 Feb;37(1):16–22. [PubMed] [Google Scholar]
  17. Kotwal G. J., Isaacs S. N., McKenzie R., Frank M. M., Moss B. Inhibition of the complement cascade by the major secretory protein of vaccinia virus. Science. 1990 Nov 9;250(4982):827–830. doi: 10.1126/science.2237434. [DOI] [PubMed] [Google Scholar]
  18. Kotwal G. J., Moss B. Vaccinia virus encodes two proteins that are structurally related to members of the plasma serine protease inhibitor superfamily. J Virol. 1989 Feb;63(2):600–606. doi: 10.1128/jvi.63.2.600-606.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mackett M., Archard L. C. Conservation and variation in Orthopoxvirus genome structure. J Gen Virol. 1979 Dec;45(3):683–701. doi: 10.1099/0022-1317-45-3-683. [DOI] [PubMed] [Google Scholar]
  20. Müller H. K., Wittek R., Schaffner W., Schümperli D., Menna A., Wyler R. Comparison of five poxvirus genomes by analysis with restriction endonucleases HindIII, BamI and EcoRI. J Gen Virol. 1978 Jan;38(1):135–147. doi: 10.1099/0022-1317-38-1-135. [DOI] [PubMed] [Google Scholar]
  21. O'Neill H. C., Blanden R. V. Mechanisms determining innate resistance to ectromelia virus infection in C57BL mice. Infect Immun. 1983 Sep;41(3):1391–1394. doi: 10.1128/iai.41.3.1391-1394.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. O'Neill H. C., Brenan M. A role for early cytotoxic T cells in resistance to ectromelia virus infection in mice. J Gen Virol. 1987 Oct;68(Pt 10):2669–2673. doi: 10.1099/0022-1317-68-10-2669. [DOI] [PubMed] [Google Scholar]
  23. O'Neill H. C. Resistance to ectromelia virus infection in mice. Analysis of H-2-linked gene effects. Arch Virol. 1991;118(3-4):253–259. doi: 10.1007/BF01314035. [DOI] [PubMed] [Google Scholar]
  24. Pickup D. J., Ink B. S., Hu W., Ray C. A., Joklik W. K. Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7698–7702. doi: 10.1073/pnas.83.20.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ray C. A., Black R. A., Kronheim S. R., Greenstreet T. A., Sleath P. R., Salvesen G. S., Pickup D. J. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992 May 15;69(4):597–604. doi: 10.1016/0092-8674(92)90223-y. [DOI] [PubMed] [Google Scholar]
  26. SCHELL K. Studies on the innate resistance of mice to infection with mousepox. I. Resistance and antibody production. Aust J Exp Biol Med Sci. 1960 Aug;38:271–288. doi: 10.1038/icb.1960.29. [DOI] [PubMed] [Google Scholar]
  27. SCHELL K. Studies on the innate resistance of mice to infection with mousepox. II. Route of inoculation and resistance; and some observations on the inheritance of resistance. Aust J Exp Biol Med Sci. 1960 Aug;38:289–299. doi: 10.1038/icb.1960.30. [DOI] [PubMed] [Google Scholar]
  28. Smith G. L., Chan Y. S. Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily. J Gen Virol. 1991 Mar;72(Pt 3):511–518. doi: 10.1099/0022-1317-72-3-511. [DOI] [PubMed] [Google Scholar]
  29. Smith G. L., Howard S. T., Chan Y. S. Vaccinia virus encodes a family of genes with homology to serine proteinase inhibitors. J Gen Virol. 1989 Sep;70(Pt 9):2333–2343. doi: 10.1099/0022-1317-70-9-2333. [DOI] [PubMed] [Google Scholar]
  30. Smith M. S., Click R. E., Plagemann P. G. Control of mouse hepatitis virus replication in macrophages by a recessive gene on chromosome 7. J Immunol. 1984 Jul;133(1):428–432. [PubMed] [Google Scholar]
  31. Terres G., Morrison S. L., Habicht G. S. A quantitative difference in the immune response between male and female mice. Proc Soc Exp Biol Med. 1968 Mar;127(3):664–667. doi: 10.3181/00379727-127-32768. [DOI] [PubMed] [Google Scholar]
  32. Traktman P. Poxviruses: an emerging portrait of biological strategy. Cell. 1990 Aug 24;62(4):621–626. doi: 10.1016/0092-8674(90)90106-o. [DOI] [PubMed] [Google Scholar]
  33. Turner P. C., Moyer R. W. The molecular pathogenesis of poxviruses. Curr Top Microbiol Immunol. 1990;163:125–151. doi: 10.1007/978-3-642-75605-4_5. [DOI] [PubMed] [Google Scholar]
  34. Wallace G. D., Buller R. M., Morse H. C., 3rd Genetic determinants of resistance to ectromelia (mousepox) virus-induced mortality. J Virol. 1985 Sep;55(3):890–891. doi: 10.1128/jvi.55.3.890-891.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weiser W., Vellisto I., Bang F. B. Congenic strains of mice susceptible and resistant to mouse hepatitis virus. Proc Soc Exp Biol Med. 1976 Sep;152(4):499–502. doi: 10.3181/00379727-152-39426. [DOI] [PubMed] [Google Scholar]
  36. Whitaker-Dowling P., Youngner J. S. Characterization of a specific kinase inhibitory factor produced by vaccinia virus which inhibits the interferon-induced protein kinase. Virology. 1984 Aug;137(1):171–181. doi: 10.1016/0042-6822(84)90020-5. [DOI] [PubMed] [Google Scholar]

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