Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus

The baboon endogenous retrovirus (BaEV) belongs to a large, widely disperse d interference group that includes the RD114 feline endogenous virus and pr imate type D retroviruses. Recently, we and another laboratory independentl y cloned a human receptor for these viruses and identified it as the human sodium-dependent neutral amino acid transporter type 2 (hASCT2). Interestin gly, mouse and rat cells are efficiently infected by BaEV but only become s usceptible to RD114 and type D retroviruses if the cells are pretreated wit h tunicamycin, an inhibitor of protein N-linked glycosylation, To investiga te this host range difference, we cloned and analyzed NIH Swiss mouse ASCT2 (mASCT2). Surprisingly, mASCT2 did not mediate BaEV infection, which impli ed that mouse cells might have an alternative receptor for this virus. In a ddition, elimination of the two N-linked oligosaccharides from mASCT2 by mu tagenesis, as substantiated by protein N-glycosidase F digestions and Weste rn immunoblotting, did not enable it to function as a receptor for RD114 or type D retroviruses. Based on these results, we found that the related ASC T1 transporters of humans and mice are efficient receptors for BaEV but are relatively inactive for RD114 and type D retroviruses, Furthermore, elimin ation of the two N-linked oligosaccharides from extracellular loop 2 of mAS CT1 by mutagenesis enabled it to function as an efficient receptor for RD11 4 and type D retroviruses, Thus, we infer that the tunicamycin-dependent in fection of mouse cells by RD114 and type D retroviruses is caused by deglyc osylation of mASCT1, which unmasks previously buried sites for viral intera ctions. In contrast, BaEV efficiently employs the glycosylated forms of mAS CT1 that occur normally in untreated mouse cells.