Cloning and characterization of a cell surface receptor for xenotropic andpolytropic murine leukemia viruses

Xenotropic and polytropic murine leukemia viruses (X-MLVs and P-MLVs) cross -interfere to various extents in non-mouse species and in wild Asian mice, suggesting that they might use a common receptor for infection. Consistent with this hypothesis, the susceptibility of some wild mice to X-MLVs has be en mapped to the P-MLV receptor locus at the distal end of mouse chromosome 1, In this study, we report the isolation and characterization of a cDNA f or the human X-MLV cell surface receptor (X-receptor) by using a human T ly mphocyte cDNA library in a retroviral vector, The predicted X-receptor cont ains 696 amino acids with multiple hydrophobic potential membrane-spanning sequences and with weak homologies to the yeast proteins SYG1, of unknown f unction, and PHO81, which has been implicated in a system that regulates tr ansport of inorganic phosphate, Expression of the X-receptor in Chinese ham ster ovary cells, which are substantially resistant to P-MLVs and to X-MLVs , made them susceptible to both of these virus groups. The mouse homologue of the X-receptor was mapped by hybridization to the distal end of chromoso me 1 at the same position as the P-MLV receptor gene Rmc1. These results st rongly support the hypothesis that a common gene encodes the receptors for X-MLVs and P-MLVs, with the human X-receptor preferentially mediating X-MLV infections and the homologous protein of inbred mice mediating only P-MLV infections. We propose that X-MLVs and P-MLVs comprise a single family of r etroviruses that have coevolved in response to diversification in X-recepto r genes of the host.