A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses

The type D simian retroviruses cause immunosuppression in macaques and have been reported as a presumptive opportunistic infection in a patient with A IDS. Previous evidence based on viral interference has strongly suggested t hat the type D simian viruses share a common but unknown cell surface recep tor with three type C viruses: feline endogenous virus (RD114), baboon endo genous virus, and avian reticuloendotheliosis virus. Furthermore, the recep tor gene for these viruses has been mapped to human chromosome 19q13.1-13.2 . We now report the isolation and characterization of a cell surface recept or for this group of retroviruses by using a human T-lymphocyte cDNA librar y in a retroviral vector. Swiss mouse fibroblasts (NIH3T3), which are natur ally resistant to RD114, were transduced with the retroviral library and th en challenged with an RD114-pseudotyped virus containing a dominant selecta ble gene for puromycin resistance. Puromycin selection yielded 12 cellular clones that were highly susceptible to a beta-galastosidase-encoding lacZ(R D114) pseudotype virus. Using PCR primers specific for vector sequences, we amplified a common 2.9 kb product from 10 positive clones. Expression of t he 2.9-kb cDNA in Chinese hamster ovary cells conferred susceptibility to R D114, baboon endogenous virus, and the type D simian retroviruses, The 2.9- kb cDNA predicted a protein of 541 amino acids that had 98% identity with t he previously cloned human Na+-dependent neutral-amino-acid transporter B-o . Accordingly, expression of the RD114 receptor in NIH 3T3 cells resulted i n enhanced cellular uptake of L-[H-3]alanine and L-[H-3]glutamine. RNA blot (Northern) analysis suggested that the RD114 receptor is widely expressed in human tissues and cell lines, including hematopoietic cells. The human B -o transporter gene has been previously mapped to 19q13.3, which is closely linked to the gene locus of the RD114 receptor.