A putative cell surface receptor for anemia-inducing feline leukemia virussubgroup C is a member of a transporter superfamily

Domestic cats infected with the horizontally transmitted feline leukemia vi rus subgroup A (FeLV-A) often produce mutants (termed FeLV-C) that bind to a distinct cell surface receptor and cause severe aplastic anemia in vivo a nd erythroblast destruction in bone marrow cultures. The major determinant for FeLV-C-induced anemia has been mapped to a small region of the surface envelope glycoprotein that is responsible for its receptor binding specific ity. Thus, erythroblast destruction may directly or indirectly result from FeLV-C binding to its receptor. To address these issues, we functionally cl oned a putative cell surface receptor for FeLV-C (FLVCR) by using a human T -lymphocyte cDNA library in a retroviral vector. Expression of the 2.0-kbp FLVCR cDNA in naturally resistant Swiss mouse fibroblasts and Chinese hamst er ovary cells caused substantial susceptibility to FeLV-C but no change in susceptibilities to FeLV-B and other retroviruses. The predicted FLVCR pro tein contains 555 amino acids and 12 hydrophobic potential membrane-spannin g sequences. Database searches indicated that FLVCR is a member of the majo r-facilitator superfamily of transporters and implied that it may transport an organic anion. RNA blot analyses showed that FLVCR mRNA is expressed in multiple hematopoietic lineages rather than specifically in erythroblasts. These results suggest that the targeted destruction of erythroblasts by Fe LV-C may derive from their greater sensitivity to this virus rather than fr om a preferential susceptibility to infection.