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

Abstract

The onset of leukaemia caused by type C retroviruses (MLV) in mice is accelerated by the emergence of recombinant polytropic or mink cell focus–forming (MCF) viruses1,2,3,4. Susceptibility to infection by polytropic/MCF and also by closely related xenotropic MLV has been mapped to Rmc1 on mouse chromosome 1 (refs 5, 6 and 7). To identify this gene, we introduced an expression cDNA library prepared from mouse NIH3T3 fibroblasts into nonpermissive hamster cells and screened these cells for acquired susceptibility to MCF viruses encoding β–galactosidase and G418 resistance. From hamster cell clones identified in the screen, we recovered a mouse cDNA that maps to Rmc1 and confers MCF MLV infection when expressed in nonpermissive cell lines. It encodes a membrane protein related to Syg1p (suppressor of yeast Gα deletion; ref. 8). The receptor–binding domain of the MCF MLV envelope protein binds specifically to Xenopus laevis oocytes that express mouse Syg1, suggesting it functions as a receptor that mediates virus entry. We also obtained the cDNA encoding human SYG1. When expressed in hamster cells, it establishes infectivity by MCF MLV as well as xenotropic MLV, which do not infect laboratory mice.

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Figure 1: The cDNA encoding susceptibility to MCF MLV infection is derived from a gene at the Rmc1 locus.
Figure 2: Susceptibility of cells that express mouse Syg1 or human SYG1 to infection by MCF or xenotropic MLVs.
Figure 3: Amino acid sequence of SYG1 proteins.
Figure 4: Envelope binding to oocytes that express Syg1.

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Acknowledgements

We thank G. Nolan for the Phoenix–Eco cell line; T. Bianca for preparing MCF–BAG virus; E. Sheppa for assistance with the manuscript; and D. Hirsch, C. Rodriquez, R. Davey, H. Tang and A. Barnett for support and advice. This work was supported by the Howard Hughes Medical Institute and NIH grant 2R01CA/AI61246–06.

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Correspondence to James M. Cunningham.

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