LP-BM5 MuLV induces in C57BL and other sensitive mouse strains a syndrome of lymphoproliferation and severe immunodeficiency, termed """"""""MAIDS"""""""". The causative virus is a replication-defective MuLV which usually requires """"""""help"""""""" by competent B-tropic MuLVs, for which Fv-1b mouse strains, like C57BL, are permissive. Strain distribution patterns in inbred mice for sensitivity and resistance to MAIDS indicate major host influences associated with alleles at Fv-1, genes of the H-2 complex, and non-MHC related genes. Influences on disease reflect regulation of helper virus infection and spread, class I MHC control, and class II MHC associated steps in pathogenesis. The most sensitive mice among Fv-1b strains are of the H-2b haplotype (H-2 haplotypes f,j,k,p,q,r and s are also associated with sensitivity) while Fv-1b H-2d strains are highly resistant. Mapping studies using intra-H-2 recombinants and transgenic mice indicate that H-2d-mediated resistance is clearly linked to the H-2D end of the region if the rest of the MHC is derived from the b haplotype. Expansion of these studies to explore the mechanism of D end resistance, to evaluate other regions of the MHC, and to clarify the pathogenesis of MAIDS reveal a very complex interaction of H-2 region genes, both class I and class II in determining degree of sensitivity or resistance. For example, F-1 hybrids of sensitive and resistant strains are sensitive, suggesting a Class II-like susceptibility;. mice of s or q haplotype which are d at H-2D are not resistant although perhaps not fully sensitive; and mutations in major histocompatibility genes at H-2K can result in acceleration or delay in the disease process. Despite the B-tropism of the ecotropic helper virus in LP-BM5 certain Fv-1n strains have been found to be relatively sensitive to MAIDS, the mechanism apparently involving utilization of endogenous MuLV.
