High susceptibility of FVB/N mice to the paralytic disease induced by ts1, a mutant of Moloney murine leukemia virus TB.
The ts1 mutant of Moloney murine leukemia virus TB causes a degenerative neurologic and immunologic disease in susceptible strains of mice. This disease syndrome is characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, generalized bodywasting, and marked thymic atrophy associated with immune deficiency. The viral genetic determinants responsible for hindlimb paralysis in BALB/c and CFW/D mice have been localized to two point mutations in the env gene: one results in a Val-25----IIe substitution in the envelope precursor polyprotein gPr80env and the other, in an Arg-430----Lys substitution in the gp70. In this report we present studies showing that FVB/N mice were highly susceptible to ts1 and exhibited the shortest and most uniform latency period of all the murine strains tested. In addition, we have found that, unlike in CFW/D and BALB/c mice, only the Val-25----IIe substitution in the gPr80env is required to induce hindlimb paralysis in FVB/N mice. Our studies show that there was enhanced replication of ts1 in all tissues of FVB/N mice and that the virus titer in the spinal cord was more than 10-fold higher in FVB/N than in BALB/c mice by 30 days postinoculation, when the clinical signs of paralysis became evident in FVB/N mice. Apparently, other host factors that do not require the Arg-430----Lys substitution allowed high levels of viral replication within the central nervous system of FVB/N mice. These results, together with the finding that 100% of FVB/N mice that were inoculated with ts1 at 5 days of age developed hindlimb paralysis at 30-60 days postinoculation, whereas only 33% of 5-day-old BALB/c mice developed hindlimb paralysis with a much longer latency period, suggest that subtle virus-host interactions determine the incidence, the latency period, and the severity of the disease caused by ts1.
Wong
P K
PK
University of Texas, M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957.
Floyd
E
E
Szurek
P F
PF
D000375:Aging; D000818:Animals; D001921:Brain / Q000382:microbiology / Q000473:pathology; D004198:Disease Susceptibility; D006824:Hybridization, Genetic; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D009154:Mutation; D010243:Paralysis / Q000382:microbiology* / Q000473:pathology; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013950:Thymus Gland / Q000382:microbiology / Q000473:pathology; D014774:Virulence; D014779:Virus Replication / Q000235:genetics