Abstract
Most inbred strains of mice, including DBA/2 (D2), are highly susceptible to the lethal effects of ectromelia virus, but C57BL/6 (B6) mice are innately resistant. Resistance is controlled by multiple, unlinked, autosomal dominant genes. Of 101 male (B6 x D2)F1 x D2 backcrossed (N2) mice, 18 died after ectromelia virus challenge and all were homozygous for the D2 allele at the proline-rich protein (Prp) locus on distal chromosome 6 (P < 0.001). This association was suggested by the patterns of susceptibility to lethal mousepox in recombinant inbred strains derived from B6 and D2 mice (D. G. Brownstein, P. N. Bhatt, L. Gras, and R. O. Jacoby, J. Virol. 65:1946-1951, 1991). The association between the Prp locus and susceptibility to lethal mousepox also held for N2 male mice that were castrated as neonates, which increased the percentage that were susceptible to 40. Spleen virus titers were significantly augmented in B6 (NK1.1+) mice depleted of asialo GM1+ or NK1.1+ cells, whereas spleen virus titers were unaffected in D2 (NK1.1-) mice depleted of asialo GM1+ cells. These results suggest that a gene or genes within the natural killer gene complex, adjacent to the Prp locus, determine strain variations in resistance to lethal ectromelia virus infection.
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- Arase H., Arase N., Nakagawa K., Good R. A., Onoé K. NK1.1+ CD4+ CD8- thymocytes with specific lymphokine secretion. Eur J Immunol. 1993 Jan;23(1):307–310. doi: 10.1002/eji.1830230151. [DOI] [PubMed] [Google Scholar]
- Azen E. A., Davisson M. T., Cherry M., Taylor B. A. Prp (proline-rich protein) genes linked to markers Es-12 (esterase-12), Ea-10 (erythrocyte alloantigen), and loci on distal mouse chromosome 6. Genomics. 1989 Oct;5(3):415–422. doi: 10.1016/0888-7543(89)90004-9. [DOI] [PubMed] [Google Scholar]
- Bhatt P. N., Jacoby R. O. Mousepox in inbred mice innately resistant or susceptible to lethal infection with ectromelia virus. I. Clinical responses. Lab Anim Sci. 1987 Feb;37(1):11–15. [PubMed] [Google Scholar]
- Brownstein D. G., Bhatt P. N., Gras L., Budris T. Serial backcross analysis of genetic resistance to mousepox, using marker loci for Rmp-2 and Rmp-3. J Virol. 1992 Dec;66(12):7073–7079. doi: 10.1128/jvi.66.12.7073-7079.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brownstein D. G., Bhatt P. N., Gras L. Ectromelia virus replication in major target organs of innately resistant and susceptible mice after intravenous infection. Arch Virol. 1993;129(1-4):65–75. doi: 10.1007/BF01316885. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Burton R. C., Smart Y. C., Koo G. C., Winn H. J. Studies on murine natural killer (NK) cells. V. Genetic analysis of NK cell markers. Cell Immunol. 1991 Jul;135(2):445–453. doi: 10.1016/0008-8749(91)90289-n. [DOI] [PubMed] [Google Scholar]
- Charley M. R., Mikhael A., Hackett J., Kumar V., Bennett M. Mechanism of anti-asialo GM1 prevention of graft-vs-host disease: identification of allo-antigen activated T cells. J Invest Dermatol. 1988 Sep;91(3):202–206. doi: 10.1111/1523-1747.ep12464858. [DOI] [PubMed] [Google Scholar]
- Dietrich W. F., Miller J. C., Steen R. G., Merchant M., Damron D., Nahf R., Gross A., Joyce D. C., Wessel M., Dredge R. D. A genetic map of the mouse with 4,006 simple sequence length polymorphisms. Nat Genet. 1994 Jun;7(2 Spec No):220–245. doi: 10.1038/ng0694supp-220. [DOI] [PubMed] [Google Scholar]
- Dietrich W., Katz H., Lincoln S. E., Shin H. S., Friedman J., Dracopoli N. C., Lander E. S. A genetic map of the mouse suitable for typing intraspecific crosses. Genetics. 1992 Jun;131(2):423–447. doi: 10.1093/genetics/131.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giorda R., Trucco M. Mouse NKR-P1. A family of genes selectively coexpressed in adherent lymphokine-activated killer cells. J Immunol. 1991 Sep 1;147(5):1701–1708. [PubMed] [Google Scholar]
- Giorda R., Weisberg E. P., Ip T. K., Trucco M. Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1. J Immunol. 1992 Sep 15;149(6):1957–1963. [PubMed] [Google Scholar]
- Habu S., Fukui H., Shimamura K., Kasai M., Nagai Y., Okumura K., Tamaoki N. In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol. 1981 Jul;127(1):34–38. [PubMed] [Google Scholar]
- 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]
- Krieg P., Amtmann E., Sauer G. The simultaneous extraction of high-molecular-weight DNA and of RNA from solid tumors. Anal Biochem. 1983 Oct 15;134(2):288–294. doi: 10.1016/0003-2697(83)90299-3. [DOI] [PubMed] [Google Scholar]
- Rajasekar R., Augustin A. Selective proliferation of gamma delta T lymphocytes exposed to high doses of ionomycin. J Immunol. 1992 Aug 1;149(3):818–824. [PubMed] [Google Scholar]
- Ryan J. C., Turck J., Niemi E. C., Yokoyama W. M., Seaman W. E. Molecular cloning of the NK1.1 antigen, a member of the NKR-P1 family of natural killer cell activation molecules. J Immunol. 1992 Sep 1;149(5):1631–1635. [PubMed] [Google Scholar]
- Scalzo A. A., Fitzgerald N. A., Simmons A., La Vista A. B., Shellam G. R. Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen. J Exp Med. 1990 May 1;171(5):1469–1483. doi: 10.1084/jem.171.5.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stitz L., Baenziger J., Pircher H., Hengartner H., Zinkernagel R. M. Effect of rabbit anti-asialo GM1 treatment in vivo or with anti-asialo GM1 plus complement in vitro on cytotoxic T cell activities. J Immunol. 1986 Jun 15;136(12):4674–4680. [PubMed] [Google Scholar]
- Suttles J., Schwarting G. A., Stout R. D. Flow cytometric analysis reveals the presence of asialo GM1 on the surface membrane of alloimmune cytotoxic T lymphocytes. J Immunol. 1986 Mar 1;136(5):1586–1591. [PubMed] [Google Scholar]
- 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]
- Wiltrout R. H., Santoni A., Peterson E. S., Knott D. C., Overton W. R., Herberman R. B., Holden H. T. Reactivity of anti-asialo GM1 serum with tumoricidal and non-tumoricidal mouse macrophages. J Leukoc Biol. 1985 May;37(5):597–614. doi: 10.1002/jlb.37.5.597. [DOI] [PubMed] [Google Scholar]
- Yang H., Yogeeswaran G., Bukowski J. F., Welsh R. M. Expression of asialo GM1 and other antigens and glycolipids on natural killer cells and spleen leukocytes in virus-infected mice. Nat Immun Cell Growth Regul. 1985;4(1):21–39. [PubMed] [Google Scholar]
- Yokoyama W. M. Recognition structures on natural killer cells. Curr Opin Immunol. 1993 Feb;5(1):67–73. doi: 10.1016/0952-7915(93)90083-5. [DOI] [PubMed] [Google Scholar]
- Yokoyama W. M., Ryan J. C., Hunter J. J., Smith H. R., Stark M., Seaman W. E. cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6. J Immunol. 1991 Nov 1;147(9):3229–3236. [PubMed] [Google Scholar]
- Ziemer M. A., Swain W. F., Rutter W. J., Clements S., Ann D. K., Carlson D. M. Nucleotide sequence analysis of a proline-rich protein cDNA and peptide homologies of rat and human proline-rich proteins. J Biol Chem. 1984 Aug 25;259(16):10475–10480. [PubMed] [Google Scholar]