Cellular and species resistance to murine amphotropic, gibbon ape, and feline subgroup C leukemia viruses is strongly influenced by receptor expression levels and by receptor masking mechanisms

Chinese hamster ovary (CHO) cells are resistant to infections by gibbon ape leukemia virus (GALV) and amphotropic murine leukemia virus (A-MLV) unless they are pretreated with tunicamycin, an inhibitor of N-linked glycosylati on. These viruses use the related sodium-phosphate symporters Pit1 and Pit2 , respectively, as receptors in nonhamster cells, and evidence has suggeste d that the corresponding transporters of CHO cells may be masked by tunicam ycin-sensitive secreted inhibitors. Although the E36 line of Chinese hamste r cells was reported to secrete the putative Pit2 inhibitor and to be sensi tive to the inhibitory CHO factors, E36 cells are highly susceptible to bot h GALV and A-MLV in the absence of tunicamycin. Moreover, expression of E36 Pit2 in CHO cells conferred tunicamycin-independent susceptibilities to bo th viruses. Based on the latter results, it was suggested that E36 Pit2 mus t functionally differ from the endogenous Pit2 of CHO cells. To test these ideas, we analyzed the receptor properties of CHO Pit1 and Pit2 in CHO cell s. Surprisingly, and counterintuitively, transfection of a CHO Pit2 express ion vector into CHO cells conferred strong susceptibility to both GALV and A-MLV, and similar overexpression of CHO Pit1 conferred susceptibility to G ALV, Thus, CHO Pit2 is a promiscuous functional receptor for both viruses, and CHO Pit1 is a functional receptor for GALV, Similarly, we found that th e natural resistance of Mus dunni tail fibroblasts to subgroup C feline leu kemia viruses (FeLV-C) was eliminated simply by overexpression of the endog enous FeLV-C receptor homologue. These results demonstrate a novel and simp le method to unmask latent retroviral receptor activities that occur in som e cells. Specifically, resistances to retroviruses that are caused by subth reshold levels of receptor expression or by stoichiometrically limited mask ing or interference mechanisms can be efficiently overcome simply by overex pressing the endogenous receptors in the same cells.