Pathogenesis of the slow disease of the central nervous system associated with wild mouse virus. III. Role of input virus and MCF recombinants in disease.
Inbred mice bearing the FV-1n marker when inoculated at birth with an ecotropic murine leukemia virus (WM 1504-E) obtained from wild mice develop a progressive central nervous system (CNS) disease manifested by hindlimb paralysis and incoordination that begins by 6 to 7 weeks of age. Studies of infected SWR/J mice at 3 days to 4 months of age indicated the following: (1) Expression of MuLV gp69/70 and p30 antigens in CNS rises beginning as early as 3 days after inoculation and increases with time. (2) Neuronal damage is evident by Day 7, and neuronal lesions develop in all mice by Day 14. (3) WM 1504-E virus can be isolated from CNS tissue by 48 hr after initiating infection. (4) Upon passage into susceptible newborn mice, the WM 1504-E isolates cause neuronal disease. (5) "Dual-tropic" mink cell focus forming (MCF) -like virus is found in splenic but not CNS tissues by 8 weeks after initiating infection. (6) MCF viruses that arise by env gene recombination between WM 1504-E and endogenous xenotropic viruses do not cause CNS disease upon inoculation into susceptible newborn mice. Similarly inoculated WM 1504-amphotropic virus (WM 1504-A) does not cause CNS disease (7). Results in SWR/J mice can be duplicated in C3H/St and C57Br/cdj mice. These observations define the wild mouse ecotropic virus as the sole infectious agent responsible and sufficient for the development of this neurologic disease. Evidently, the disease from this "slow virus infection" begins early in life shortly after introduction of the infectious agent, but becomes clinically apparent only as neuronal destruction accumulates over the lifetime of the host.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000382:microbiology; D002460:Cell Line; D002493:Central Nervous System Diseases / Q000382:microbiology*; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008907:Mink; D011995:Recombination, Genetic; D012897:Slow Virus Diseases / Q000382:microbiology*; D013116:Spinal Cord / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D014779:Virus Replication
D000956:Antigens, Viral