Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1985 Sep;55(3):788–795. doi: 10.1128/jvi.55.3.788-795.1985

Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice.

D L Lodmell, L C Ewalt
PMCID: PMC255063  PMID: 4020967

Abstract

Seven strains of mice were examined to determine why susceptibility differences and variations in clinical central nervous system (CNS) disease occurred among these animals after intraperitoneal inoculation of street rabies virus (SRV). Trace experiments for infectious virus indicated that these differences were associated with restriction of virus replication within the CNS. Limitation of viral replication appeared to correlate with the antibody response in that prominent serum anti-SRV neutralizing antibody titers were detected in resistant strains, whereas susceptible strains produced minimal amounts of antibody until their death. The importance of the immune response was reaffirmed with cyclophosphamide studies in that all resistant SJL/J mice died after immunosuppressive treatment. In contrast, cyclophosphamide-treated SJL/J mice whose immune systems were reconstituted with either unfractionated immune spleen cells or with sera 24 h after SRV inoculation survived a lethal dose of SRV. More importantly, immunosuppressed SJL/J and immunodeficient athymic mice were protected when reconstituted with immune serum 72 h after SRV inoculation, a time in which infectious virus was detected in the spinal cords of some mice but was not present in the peritoneal cavity. Additional studies showed that antibody in the cerebrospinal fluid was unimportant in the resistance of mouse strains which remained clinically asymptomatic, but it appeared to be associated with the survival of mice which developed clinical CNS disease. Furthermore, CNS resistance to intranasal or intracerebral inoculation with challenge virus standard rabies virus developed as early as 5 days post-intraperitoneal inoculation of SRV.

Full text

PDF
788

Selected References

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

  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Bell J. F., Moore G. J., Raymond G. H. Protracted survival of a rabies-infected insectivorous bat after infective bite. Am J Trop Med Hyg. 1969 Jan;18(1):61–66. [PubMed] [Google Scholar]
  6. Blenden D. C., Bell J. F., Tsao A. T., Umoh J. U. Immunofluorescent examination of the skin of rabies-infected animals as a means of early detection of rabies virus antigen. J Clin Microbiol. 1983 Sep;18(3):631–636. doi: 10.1128/jcm.18.3.631-636.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cox J. H., Dietzschold B., Schneider L. G. Rabies virus glycoprotein. II. Biological and serological characterization. Infect Immun. 1977 Jun;16(3):754–759. doi: 10.1128/iai.16.3.754-759.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dietzschold B., Wiktor T. J., Macfarlan R., Varrichio A. Antigenic structure of rabies virus glycoprotein: ordering and immunological characterization of the large CNBr cleavage fragments. J Virol. 1982 Nov;44(2):595–602. doi: 10.1128/jvi.44.2.595-602.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dietzschold B., Wiktor T. J., Wunner W. H., Varrichio A. Chemical and immunological analysis of the rabies soluble glycoprotein. Virology. 1983 Jan 30;124(2):330–337. doi: 10.1016/0042-6822(83)90349-5. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Fekadu M. Atypical rabies in dogs in Ethiopia. Ethiop Med J. 1972 Jul;10(3):79–86. [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. Fekadu M., Shaddock J. H., Baer G. M. Intermittent excretion of rabies virus in the saliva of a dog two and six months after it had recovered from experimental rabies. Am J Trop Med Hyg. 1981 Sep;30(5):1113–1115. doi: 10.4269/ajtmh.1981.30.1113. [DOI] [PubMed] [Google Scholar]
  15. Flamand A., Wiktor T. J., Koprowski H. Use of hybridoma monoclonal antibodies in the detection of antigenic differences between rabies and rabies-related virus proteins. II. The glycoprotein. J Gen Virol. 1980 May;48(1):105–109. doi: 10.1099/0022-1317-48-1-105. [DOI] [PubMed] [Google Scholar]
  16. Griffin D. E., Narayan O., Bukowski J. F., Adams R. J., Cohen S. R. The cerebrospinal fluid in visna, a slow viral disease of sheep. Ann Neurol. 1978 Sep;4(3):212–218. doi: 10.1002/ana.410040304. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. Larghi O. P., González E., Held J. R. Evaluation of the corneal test as a laboratory method for rabies diagnosis. Appl Microbiol. 1973 Feb;25(2):187–189. doi: 10.1128/am.25.2.187-189.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lipton H. L., Gonzalez-Scarano F. Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response. J Infect Dis. 1978 Feb;137(2):145–151. doi: 10.1093/infdis/137.2.145. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Lodmell D. L., Chesebro B. Murine resistance to street rabies virus: genetic analysis by testing second-backcross progeny and verification of allelic resistance genes in SJL/J and CBA/J mice. J Virol. 1984 May;50(2):359–362. doi: 10.1128/jvi.50.2.359-362.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lodmell D. L. Genetic control of resistance to street rabies virus in mice. J Exp Med. 1983 Feb 1;157(2):451–460. doi: 10.1084/jem.157.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mifune K., Takeuchi E., Napiorkowski P. A., Yamada A., Sakamoto K. Essential Role of T cells in the postexposure prophylaxis of rabies in mice. Microbiol Immunol. 1981;25(9):895–904. doi: 10.1111/j.1348-0421.1981.tb00094.x. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Murphy F. A. Rabies pathogenesis. Arch Virol. 1977;54(4):279–297. doi: 10.1007/BF01314774. [DOI] [PubMed] [Google Scholar]
  30. Nilsson M. R., Sant'anna O. A., Siqueira M., Nilsson T. T., Gennari M. Rabies virus immunity in genetically selected high- and low-responder lines of mice. Infect Immun. 1979 Jul;25(1):23–26. doi: 10.1128/iai.25.1.23-26.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pereira C. A., Nozaki-Renard J. N., Schwartz J., Eyquem A., Atanasiu P. Cytotoxicity reactions against target cells infected with rabies virus. J Virol Methods. 1982 Oct;5(2):75–83. doi: 10.1016/0166-0934(82)90084-2. [DOI] [PubMed] [Google Scholar]
  32. Perl D. P., Bell J. F., Moore G. J. Chronic recrudescent rabies in a cat. Proc Soc Exp Biol Med. 1977 Sep;155(4):540–548. doi: 10.3181/00379727-155-39847. [DOI] [PubMed] [Google Scholar]
  33. Reddehase M. J., Cox J. H., Koszinowski U. H. Frequency analysis of cytolytic T cell precursors (CTL-P) generated in vivo during lethal rabies infection of mice. I. Distinction of CTL-P with different interleukin 2 sensitivity. Eur J Immunol. 1982 Jun;12(6):519–523. doi: 10.1002/eji.1830120613. [DOI] [PubMed] [Google Scholar]
  34. SIKES R. K. Pathogenesis of rabies in wildlife. I. Comparative effect of varying doses of rabies virus inoculated into foxes and skunks. Am J Vet Res. 1962 Sep;23:1041–1047. [PubMed] [Google Scholar]
  35. Schneider L. G. The cornea test; a new method for the intra-vitam diagnosis of rabies. Zentralbl Veterinarmed B. 1969 Feb;16(1):24–31. doi: 10.1111/j.1439-0450.1969.tb00085.x. [DOI] [PubMed] [Google Scholar]
  36. Smith A. L., Tignor G. H., Mifune K., Motohashi T. Isolation and assay of rabies serogroup viruses in CER cells. Intervirology. 1977;8(2):92–99. doi: 10.1159/000148883. [DOI] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. Smith J. S., Yager P. A., Baer G. M. A rapid reproducible test for determining rabies neutralizing antibody. Bull World Health Organ. 1973 May;48(5):535–541. [PMC free article] [PubMed] [Google Scholar]
  40. Smith W. B., Blenden D. C., Fuh T. H., Hiler L. Diagnosis of rabies by immunofluorescent staining of frozen sections of skin. J Am Vet Med Assoc. 1972 Dec 1;161(11):1495–1501. [PubMed] [Google Scholar]
  41. 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]
  42. Turk J. L., Parker D. The effect of cyclophosphamide on the immune response. J Immunopharmacol. 1979;1(2):127–137. doi: 10.3109/08923977909026368. [DOI] [PubMed] [Google Scholar]
  43. Turner G. S. Immunoglobulin (IgG) and (IgM) antibody responses to rabies vaccine. J Gen Virol. 1978 Sep;40(3):595–604. doi: 10.1099/0022-1317-40-3-595. [DOI] [PubMed] [Google Scholar]
  44. VAUGHN J. B., GERHARDT P., PATERSON J. C. Excretion of street rabies virus in saliva of cats. JAMA. 1963 Jun 1;184:705–708. doi: 10.1001/jama.1963.73700220001013. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. 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]
  47. Wiktor T. J., György E., Schlumberger D., Sokol F., Koprowski H. Antigenic properties of rabies virus components. J Immunol. 1973 Jan;110(1):269–276. [PubMed] [Google Scholar]
  48. YURKOVSKY A. M. Hydrophobia following the bite of apparently healthy dogs. J Hyg Epidemiol Microbiol Immunol. 1962;6:73–78. [PubMed] [Google Scholar]

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

RESOURCES