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. 1983 Feb 1;157(2):451–460. doi: 10.1084/jem.157.2.451

Genetic control of resistance to street rabies virus in mice

PMCID: PMC2186935  PMID: 6822785

Abstract

Resistance to intraperitoneally inoculated street rabies virus (SRV) in mice was shown to be under genetic control. SJL/J, CBA/J, DBA/2J, and BALB/cAn mice were resistant, whereas A/WySn/J and A.SW/SnJ mice were susceptible. In addition, female mice of the resistant BALB/cAn and DBA/2J strains were more resistant than their male counterparts. Resistance was not controlled solely by the major histocompatibility locus because susceptible A.SW/SnJ and resistant SJL/J mice have the same H-2S haplotype. Challenge of F1 hybrids produced by crossing resistant and susceptible strains indicated resistance was dominant (97% survivors). Inoculation of backcross mice produced by mating F1 hybrids with susceptible parents showed that one and/or two genes controlled susceptibility. Furthermore, inoculation of SRV obtained from six different animals indicated that differences in strain susceptibilities were not dependent on the SRV isolate. Genetic control of resistance to SRV was, however, abrogated by intracerebral inoculation of virus. Resistant strains of mice were detected that either remained asymptomatic or, in contrast, developed signs of clinical disease, but disease failed to progress and they survived. The recognition of resistant and susceptible strains of mice, differences in female-male resistance within the same resistant strain, as well as dissimilar clinical responses in different resistant mouse strains to intraperitoneally inoculated SRV provide promising probes for investigation of host resistance and mechanisms for survival after onset of clinical rabies.

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Selected References

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  1. Andersen A. A., Hanson R. P. Influence of sex and age on natural resistance to St. Louis encephalitis virus infection in mice. Infect Immun. 1974 Jun;9(6):1123–1125. doi: 10.1128/iai.9.6.1123-1125.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arko R. J., Schneider L. G., Baer G. M. Nonfatal canine rabies. Am J Vet Res. 1973 Jul;34(7):937–938. [PubMed] [Google Scholar]
  3. BELL J. F. ABORTIVE RABIES INFECTION. I. EXPERIMENTAL PRODUCTION IN WHITE MICE AND GENERAL DISCUSSION. J Infect Dis. 1964 Jun;114:249–257. doi: 10.1093/infdis/114.3.249. [DOI] [PubMed] [Google Scholar]
  4. BOLIN V. S. Survival of a guinea pig following infection with street rabies virus; a case report. J Am Vet Med Assoc. 1959 Jan 15;134(2):90–92. [PubMed] [Google Scholar]
  5. Baer G. M., Cleary W. F., Díaz A. M., Perl D. F. Characteristics of 11 rabies virus isolates in mice: titers and relative invasiveness of virus, incubation period of infection, and survival of mice with sequelae. J Infect Dis. 1977 Sep;136(3):336–345. doi: 10.1093/infdis/136.3.336. [DOI] [PubMed] [Google Scholar]
  6. Baer G. M., Olson H. R. Recovery of pigs from rabies. J Am Vet Med Assoc. 1972 Apr 15;160(8):1127–1128. [PubMed] [Google Scholar]
  7. Baer G. M., Shaddock J. H., Moore S. A., Yager P. A., Baron S. S., Levy H. B. Successful prophylaxis against rabies in mice and Rhesus monkeys: the interferon system and vaccine. J Infect Dis. 1977 Aug;136(2):286–291. doi: 10.1093/infdis/136.2.286. [DOI] [PubMed] [Google Scholar]
  8. Berjivich S., Ressel M. Effect of sex on susceptibility of adult mice to coxsackie B1 virus infection. Arch Gesamte Virusforsch. 1967;22(1):246–251. doi: 10.1007/BF01240519. [DOI] [PubMed] [Google Scholar]
  9. Cohn D. A. High sensitivity to androgen as a contributing factor in sex differences in the immune response. Arthritis Rheum. 1979 Nov;22(11):1218–1233. doi: 10.1002/art.1780221109. [DOI] [PubMed] [Google Scholar]
  10. DEAN D. J., SHERMAN I. Potency of commercial rabies vaccine used in man. Public Health Rep. 1962 Aug;77:705–710. [PMC free article] [PubMed] [Google Scholar]
  11. Dubois-Dalcq M., Hooghe-Peters E. L., Lazzarini R. A. Antibody-induced modulation of rhabdovirus infection of neurons in vitro. J Neuropathol Exp Neurol. 1980 Sep;39(5):507–522. doi: 10.1097/00005072-198009000-00001. [DOI] [PubMed] [Google Scholar]
  12. Faulkner G., Dubois-Dalcq M., Hooghe-Peters E., McFarland H. F., Lazzarini R. A. Defective interfering particles modulate VSV infection of dissociated neuron cultures. Cell. 1979 Aug;17(4):979–991. doi: 10.1016/0092-8674(79)90337-4. [DOI] [PubMed] [Google Scholar]
  13. Fekadu M., Baer G. M. Recovery from clinical rabies of 2 dogs inoculated with a rabies virus strain from Ethiopia. Am J Vet Res. 1980 Oct;41(10):1632–1634. [PubMed] [Google Scholar]
  14. Fenje P., Postic B. Protection of rabbits against experimental rabies of poly I-poly C. Nature. 1970 Apr 11;226(5241):171–172. doi: 10.1038/226171a0. [DOI] [PubMed] [Google Scholar]
  15. Ferris D. H., Badiali L., Abou-Youssef M., Beamer P. D. A note on experimental rabies in the donkey. Cornell Vet. 1968 Apr;58(2):270–277. [PubMed] [Google Scholar]
  16. Friedman S. B., Grota L. J., Glasgow L. A. Differential susceptibility of male and female mice to encephalomyocarditis virus: effects of castration, adrenalectomy, and the administration of sex hormones. Infect Immun. 1972 May;5(5):637–644. doi: 10.1128/iai.5.5.637-644.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. HURST E. W., MELVIN P. A., THORP J. M. The influence of sex on equine encephalomyelitis in the mouse and on its treatment with mepacrine. J Comp Pathol. 1960 Jul;70:346–360. doi: 10.1016/s0368-1742(60)80033-1. [DOI] [PubMed] [Google Scholar]
  18. Harmon M. W., Janis B. Therapy of murine rabies after exposure: efficacy of polyriboinosinic-polyribocytidylic acid alone and in combination with three rabies vaccines. J Infect Dis. 1975 Sep;132(3):241–249. doi: 10.1093/infdis/132.3.241. [DOI] [PubMed] [Google Scholar]
  19. Hattwick M. A., Weis T. T., Stechschulte C. J., Baer G. M., Gregg M. B. Recovery from rabies. A case report. Ann Intern Med. 1972 Jun;76(6):931–942. doi: 10.7326/0003-4819-76-6-931. [DOI] [PubMed] [Google Scholar]
  20. Hilfenhaus J., Weinmann E., Majer M., Barth R., Jaeger O. Administration of human interferon to rabies virus-infected monkeys after exposure. J Infect Dis. 1977 May;135(5):846–849. [PubMed] [Google Scholar]
  21. Huang A. S., Baltimore D. Defective viral particles and viral disease processes. Nature. 1970 Apr 25;226(5243):325–327. doi: 10.1038/226325a0. [DOI] [PubMed] [Google Scholar]
  22. KITSELMAN C. H. RECOVERY OF A RAT FROM EXPERIMENTALLY INDUCED RABIES. J Am Vet Med Assoc. 1964 May 15;144:1113–1114. [PubMed] [Google Scholar]
  23. Kawai A., Matsumoto S. Interfering and noninterfering defective particles generated by a rabies small plaque variant virus. Virology. 1977 Jan;76(1):60–71. doi: 10.1016/0042-6822(77)90282-3. [DOI] [PubMed] [Google Scholar]
  24. Lodmell D. L., Arai Y. T., Ewalt L. C. Influence of cell type and virus upon lysis of rabies virus-infected cells by antibody and complement. Arch Virol. 1981;70(2):147–155. doi: 10.1007/BF01315008. [DOI] [PubMed] [Google Scholar]
  25. Lodmell D. L., Bell J. F., Moore G. J., Raymond G. H. Comparative study of abortive and nonabortive rabies in mice. J Infect Dis. 1969 Jun;119(6):569–580. doi: 10.1093/infdis/119.6.569. [DOI] [PubMed] [Google Scholar]
  26. Miller A., Morse H. C., 3rd, Winkelstein J., Nathanson N. The role of antibody in recovery from experimental rabies. I. Effect of depletion of B and T cells. J Immunol. 1978 Jul;121(1):321–326. [PubMed] [Google Scholar]
  27. Murphy F. A. Rabies pathogenesis. Arch Virol. 1977;54(4):279–297. doi: 10.1007/BF01314774. [DOI] [PubMed] [Google Scholar]
  28. Public Health Weekly Reports for AUGUST 16, 1940. Public Health Rep. 1940 Aug 16;55(33):1473–1516. [PMC free article] [PubMed] [Google Scholar]
  29. Smith J. S., McCelland C. L., Reid F. L., Baer G. M. Dual role of the immune response in street rabiesvirus infection of mice. Infect Immun. 1982 Jan;35(1):213–221. doi: 10.1128/iai.35.1.213-221.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith J. S. Mouse model for abortive rabies infection of the central nervous system. Infect Immun. 1981 Jan;31(1):297–308. doi: 10.1128/iai.31.1.297-308.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stewart W. E., 2nd, Sulkin S. E. Interferon production in hamsters experimentally infected with rabies virus. Proc Soc Exp Biol Med. 1966 Dec;123(3):650–654. doi: 10.3181/00379727-123-31568. [DOI] [PubMed] [Google Scholar]
  32. WHEATER D. W., HURST E. W. The effect of sex on bacterial infections in mice and on the chemotherapy of one of them. J Pathol Bacteriol. 1961 Jul;82:117–130. doi: 10.1002/path.1700820115. [DOI] [PubMed] [Google Scholar]
  33. WILLOUGHBY D. S., WATSON D. W. HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. II. INFLUENCE OF SEX ON THE SUSCEPTIBILITY OF INBRED MICE TOWARD STREPTOCOCCAL INFECTION. J Bacteriol. 1964 Jun;87:1457–1461. doi: 10.1128/jb.87.6.1457-1461.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wiktor T. J., Dietzschold B., Leamnson R. N., Koprowski H. Induction and biological properties of defective interfering particles of rabies virus. J Virol. 1977 Feb;21(2):626–635. doi: 10.1128/jvi.21.2.626-635.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wiktor T. J., Doherty P. C., Koprowski H. In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus. Proc Natl Acad Sci U S A. 1977 Jan;74(1):334–338. doi: 10.1073/pnas.74.1.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wiktor T. J., Doherty P. C., Koprowski H. Suppression of cell-mediated immunity by street rabies virus. J Exp Med. 1977 Jun 1;145(6):1617–1622. doi: 10.1084/jem.145.6.1617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wiktor T. J., Koprowski H. Monoclonal antibodies against rabies virus produced by somatic cell hybridization: detection of antigenic variants. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3938–3942. doi: 10.1073/pnas.75.8.3938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wiktor T. J., Postic B., Ho M., Koprowski H. Role of interferon induction in the protective activity of rabies vaccines. J Infect Dis. 1972 Oct;126(4):408–418. doi: 10.1093/infdis/126.4.408. [DOI] [PubMed] [Google Scholar]

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