A unique sequence related to the ecotropic murine leukemia virus is associated with the Fv-4 resistance gene

Several strains of laboratory and wild-derived mice from Japan carry the dominant allele at the Fv-4 locus (Fv-4r) that is responsible for resistance to infection by exogenous ecotropic murine leukemia virus. We have used blot hybridization with a probe specific for the ecotropic viral envelope to show that a unique envelope-reactive sequence is present in the Japanese mouse Mus musculus molossinus and in four independently derived partially congeneic strains carrying Fv-4r. Analysis of 31 backcross mice shows complete concordance between inheritance of this fragment and resistance to Friend virus complex-induced erythroblastosis. Inheritance of this sequence also suppresses spontaneous expression of the endogenous ecotropic viruses carried by M. m. molossinus. Restriction enzyme analysis shows that the Fv-4r-associated sequence is different from the full-length ecotropic proviruses of laboratory mice. Infectious virus cannot be induced from mice carrying only the Fv-4r-associated sequence. Examination of other wild-derived mice resistant to Friend virus complex shows that Mus cervicolor cervicolor also contains the Fv-4r sequence. Our data indicate that a unique or incomplete provirus containing ecotropic envelope-related sequences is responsible for Fv-4-mediated resistance to both exogenous and endogenous ecotropic virus in various Asian mice.