Receptor-mediated interference mechanism responsible for resistance to polytropic leukemia viruses in Mus castaneus

The Asian mouse Mus castaneus is resistant to infection by the polytropic m ink cell focus-inducing (MCF) subgroup of murine leukemia viruses (MuLVs). Genetic crosses showed this recessive resistance to be governed by a single gene that maps at or near the gene encoding the polytropic viral receptor, Rmc1, To investigate this resistance, we mated M, castaneus with mice carr ying the wild mouse Sxv variant of the Rmc1 receptor that allows infection by xenotropic as well as polytropic virus. Unlike other F-1 hybrids of M, c astaneus, these F-1 mice were resistant to both xenotropic and polytropic c lasses of MuLVs, Analysis of backcrossed progeny of the F-1 hybrids mated t o Sxv mice indicates that resistance is due to inheritance of two M. castan eus genes, Cells from individual backcross mice were also examined for cell surface antigen by fluorescence-activated cell sorter analysis with monocl onal antibodies reactive with xenotropic or MCF virus env glycoproteins. A correlation was observed between virus resistance and antigen, suggesting t hat virus resistance is due to expression of endogenous viral envelope gene s that interfere with infection by exogenous virus. Since the inbred strain Rmc1 receptor remains functional in the presence of these M, castaneus gen es, and since M, castaneus contains multiple copies of xenotropic MuLV env genes, we suggest that these resistance genes control expression of xenotro pic env glycoprotein that interferes with exogenous virus in cells containi ng the Sn, variant of Rmc1.