Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice.
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.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000134:cerebrospinal fluid; D002490:Central Nervous System / Q000382:microbiology; D003520:Cyclophosphamide / Q000494:pharmacology; D007116:Immunization, Passive; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D008819:Mice, Nude; D011818:Rabies / Q000276:immunology*; D011820:Rabies virus / Q000254:growth & development; D013045:Species Specificity; D013997:Time Factors; D014779:Virus Replication
D000914:Antibodies, Viral; D003520:Cyclophosphamide