Abstract
DBA/2 (D2) mice are susceptible and C57BL/6 (B6) mice are resistant to lethal mousepox. A congenic resistant strain, D2.B6-Rmp-4r (D2.R4), was developed by serially backcrossing male mice that survived ectromelia virus infection with D2 mice, beginning with (B6 x D2)F1 mice. Male D2.R4 mice were at least 300-fold more resistant to lethal mousepox than male D2 mice. Female D2.R4 mice were 100-fold more resistant than male D2.R4 mice and 500-fold more resistant than female D2 mice. Neonatal gonadectomy prevented development of resistance in D2.R4 mice of both sexes. Differences in resistance between strains and between sexes correlated with restriction of virus replication in spleen and liver, but gender differences were less evident in liver than in spleen. High-resolution interval mapping of the 19 autosomes of D2.R4 mice using dispersed informative microsatellites as marker loci revealed a segment of distal chromosome 1 to be of B6 origin. Haplotypes for a marker locus, D1Mit57, from the differential segment were determined in (D2.R4 x D2)F1 x D2 backcross mice, which were then infected with ectromelia virus. Significantly more heterozygotes than homozygotes survived ectromelia virus infection in both sexes. Whereas nearly all surviving males were heterozygotes, 44% of surviving females were homozygotes. These results indicate that resistance in D2.R4 mice is determined by a gonad-dependent gene on distal chromosome 1, provisionally named Rmp-4, and by an ovary-dependent factor that is not genetically linked to Rmp-4.
Full Text
The Full Text of this article is available as a PDF (384.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- 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]
- Buller R. M., Chakrabarti S., Cooper J. A., Twardzik D. R., Moss B. Deletion of the vaccinia virus growth factor gene reduces virus virulence. J Virol. 1988 Mar;62(3):866–874. doi: 10.1128/jvi.62.3.866-874.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Buller R. M., Potter M., Wallace G. D. Variable resistance to ectromelia (mousepox) virus among genera of Mus. Curr Top Microbiol Immunol. 1986;127:319–322. doi: 10.1007/978-3-642-71304-0_38. [DOI] [PubMed] [Google Scholar]
- Czuprynski C. J., Canono B. P., Henson P. M., Campbell P. A. Genetically determined resistance to listeriosis is associated with increased accumulation of inflammatory neutrophils and macrophages which have enhanced listericidal activity. Immunology. 1985 Jul;55(3):511–518. [PMC free article] [PubMed] [Google Scholar]
- Delano M. L., Brownstein D. G. Innate resistance to lethal mousepox is genetically linked to the NK gene complex on chromosome 6 and correlates with early restriction of virus replication by cells with an NK phenotype. J Virol. 1995 Sep;69(9):5875–5877. doi: 10.1128/jvi.69.9.5875-5877.1995. [DOI] [PMC free article] [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]
- 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]
- Kelner G. S., Kennedy J., Bacon K. B., Kleyensteuber S., Largaespada D. A., Jenkins N. A., Copeland N. G., Bazan J. F., Moore K. W., Schall T. J. Lymphotactin: a cytokine that represents a new class of chemokine. Science. 1994 Nov 25;266(5189):1395–1399. doi: 10.1126/science.7973732. [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]
- Lander E. S., Schork N. J. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. doi: 10.1126/science.8091226. [DOI] [PubMed] [Google Scholar]
- 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]
- Mathew P. A., Garni-Wagner B. A., Land K., Takashima A., Stoneman E., Bennett M., Kumar V. Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells. J Immunol. 1993 Nov 15;151(10):5328–5337. [PubMed] [Google Scholar]
- Mortensen R. F., Le P. T., Taylor B. A. Mouse serum amyloid P-component (SAP) levels controlled by a locus on chromosome 1. Immunogenetics. 1985;22(4):367–375. doi: 10.1007/BF00430920. [DOI] [PubMed] [Google Scholar]
- Naylor D. H., Cinader B. Inheritance, hormonal regulation and properties of polymorphic murine antigens Mud1 and Mud2. Int Arch Allergy Appl Immunol. 1970;39(5-6):511–539. doi: 10.1159/000230380. [DOI] [PubMed] [Google Scholar]
- Opalka B., Kölsch E. Evidence for a new lymphocyte-stimulating determinant (Lsd) detected by alloreactive T cell lines. Eur J Immunol. 1983 Jan;13(1):24–30. doi: 10.1002/eji.1830130107. [DOI] [PubMed] [Google Scholar]
- Opdenakker G., Snoddy J., Choubey D., Toniato E., Pravtcheva D. D., Seldin M. F., Ruddle F. H., Lengyel P. Interferons as gene activators: a cluster of six interferon-activatable genes is linked to the erythroid alpha-spectrin locus on murine chromosome 1. Virology. 1989 Aug;171(2):568–578. doi: 10.1016/0042-6822(89)90626-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Pizcueta P., Luscinskas F. W. Monoclonal antibody blockade of L-selectin inhibits mononuclear leukocyte recruitment to inflammatory sites in vivo. Am J Pathol. 1994 Aug;145(2):461–469. [PMC free article] [PubMed] [Google Scholar]
- Roseman N. A., Slabaugh M. B. The vaccinia virus HindIII F fragment: nucleotide sequence of the left 6.2 kb. Virology. 1990 Oct;178(2):410–418. doi: 10.1016/0042-6822(90)90338-r. [DOI] [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]
- Seldin M. F., Morse H. C., LeBoeuf R. C., Steinberg A. D. Establishment of a molecular genetic map of distal mouse chromosome 1: further definition of a conserved linkage group syntenic with human chromosome 1q. Genomics. 1988 Jan;2(1):48–56. doi: 10.1016/0888-7543(88)90108-5. [DOI] [PubMed] [Google Scholar]
- Siegelman M. H., Cheng I. C., Weissman I. L., Wakeland E. K. The mouse lymph node homing receptor is identical with the lymphocyte cell surface marker Ly-22: role of the EGF domain in endothelial binding. Cell. 1990 May 18;61(4):611–622. doi: 10.1016/0092-8674(90)90473-r. [DOI] [PubMed] [Google Scholar]
- Stevenson M. M., Gervais F., Skamene E. Natural resistance to listeriosis: role of host inflammatory responsiveness. Clin Invest Med. 1984;7(4):297–301. [PubMed] [Google Scholar]
- 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]
- 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]
- Twardzik D. R., Brown J. P., Ranchalis J. E., Todaro G. J., Moss B. Vaccinia virus-infected cells release a novel polypeptide functionally related to transforming and epidermal growth factors. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5300–5304. doi: 10.1073/pnas.82.16.5300. [DOI] [PMC free article] [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]
- Weir J. P., Bajszár G., Moss B. Mapping of the vaccinia virus thymidine kinase gene by marker rescue and by cell-free translation of selected mRNA. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1210–1214. doi: 10.1073/pnas.79.4.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong Y. W., Williams A. F., Kingsmore S. F., Seldin M. F. Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3. J Exp Med. 1990 Jun 1;171(6):2115–2130. doi: 10.1084/jem.171.6.2115. [DOI] [PMC free article] [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]