Studies of genetically based sensitivity and resistance to murine leukemia virus (MuLV) infection and disease induction have centered on BM5 MuLV and MAIDS. For the disease-inducing defective BM5 genome (BM5def) pseudotyped by B-tropic helper virus, the most sensitive mice are those of Fv-1(b) genotype and H-2 haplotypes b, f, k, p, q, r, or s. In the insensitive H-2(d) and H-2(a) strains, resistance is linked to the D end of H-2, suggesting a major role for a protective immune response that is CTL mediated and thus affected by MHC Class I genes and CD8+ T cells. Depletion of the CD8+ T cell population in mice of highly resistant strain A/J, following infection with BM5 MuLV, resulted in development of moderately severe disease, increased replication of ecotropic helper virus, and integration of the BM5def genome in cellular DNA. Neither disease nor defective virus integration was observed in mice depleted of CD4+ T cells, IL-2 or IFN-Gamma, although some mice replicated ecotropic virus at a higher level than control infected mice. Further, mutations in both D and K region Class I genes of C57BL (sensitive) mice can alter the course of disease, and tests of C57BL homozygous for a disrupted Beta2- microglobulin transgene and thereby deficient for MHC Class I suggest that such mice have enhanced susceptibility to MAIDS. Much evidence indicates that MAIDS is an immunopathologic condition, in which the interaction of MHC Class II genes, CD4+ T cells, and BM5def viral antigen are required and in which Class II region effects can influence Class I H-2D-regulated resistance. The results of testing a large number of H-2 recombinant and mutant mouse strains for sensitivity to MAIDS show that I-EAlphaEBeta+ mice are the most sensitive while I-EAlphaEBeta- strains are uniformly sensitive.
