CHIMERAS OF RECEPTORS FOR GIBBON APE LEUKEMIA-VIRUS FELINE LEUKEMIA-VIRUS-B AND AMPHOTROPIC MURINE LEUKEMIA-VIRUS REVEAL DIFFERENT MODES OFRECEPTOR RECOGNITION BY RETROVIRUS

Glvr1 encodes the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related gene Glvr2 encodes the human receptor for amphotropic murine leukemia virus es (A-MLVs). The two proteins are 62% identical in their amino acid se quences and are predicted to have 10 transmembrane domains and five ex tracellular loops. A stretch of nine amino acids (region A) in the pre dicted fourth extracellular loop was previously shown to be critical f or the function of Glvr1 as receptor for GALV and FeLV-B. Glvr1 and -2 show clusters of amino acid differences in several of their predicted extracellular loops, with the highest degree of divergence in region A. Chimeras were made between the two genes to further investigate the role of Glvr1 region A in defining receptor specificity for GALV and FeLV-B and to map which regions of Glvr2 control receptor specificity for A-MLVs. Region A from Glvr1 was sufficient to confer receptor spec ificity for GALV upon Glvr2, with the same chimera failing to act as a receptor for FeLV-B. However, introduction of additional N- or C-term inal Glvr1-encoding sequences in addition to Glvr1 region A-encoding s equences resulted in functional FeLV-B receptors. Therefore, FeLV-B is dependent on Glvr1 sequences outside region A for infectivity. The re ceptor specificity of Glvr2 for A-MLV could not be mapped to a single critical region; rather, N-terminal as well as C-terminal Glvr2-encodi ng sequences could confer specificity for A-MLV infection upon Glvr1. Surprisingly, though GALV/FeLV-B and A-MLV belong to different interfe rence groups, some chimeras functioned as receptors for all three viru ses.