Receptors for polytropic and xenotropic mouse leukaemia viruses encoded bya single gene at Rmc1

The onset of leukaemia caused by type C retroviruses (MLV) in mice is accel erated by the emergence of recombinant polytropic or mink cell focus-formin g (MCF) viruses(1-4). Susceptibility to infection by polytropic/MCF and als o by closely related xenotropic MLV has been mapped to Rmc1 on mouse chromo some 1 (refs 5-7). To identify this gene, we introduced an expression cDNA library prepared from mouse NIH3T3 fibroblasts into nonpermissive hamster c ells and screened these cells for acquired susceptibility to MCF viruses en coding beta-galactosidase and G418 resistance. From hamster cell clones ide ntified in the screen, we recovered a mouse cDNA that maps to Rmc1 and conf ers MCF MLV infection when expressed in nonpermissive cell lines. It encode s a membrane protein related to Syg1p (suppressor of yeast G alpha deletion ; ref. 8), The receptor-binding domain of the MCF MLV envelope protein bind s specifically to Xenopus laevis oocytes that express mouse Syg1, suggestin g it functions as a receptor that mediates virus entry. We also obtained th e cDNA encoding human SYG1. When expressed in hamster cells, it establishes infectivity by MCF MLV as well as xenotropic MLV, which do not infect labo ratory mice.