3 DISTINCT ENVELOPE DOMAINS, VARIABLY PRESENT IN SUBGROUP-B FELINE LEUKEMIA-VIRUS RECOMBINANTS, MEDIATE PIT1 AND PIT2 RECEPTOR RECOGNITION

Subgroup B feline leukemia viruses (FeLV-Bs) evolve from subgroup A Fe LV (FeLV-A) by recombining with portions of endogenous FeLV envelope s equences in the cat genome, The replication properties of FeLV-B are d istinct from those of FeLV-A; FeLV-B infects many nonfeline cell lines and recognizes the human Pit1 (HuPit1) receptor, whereas FeLV-A infec ts primarily feline cells, using a distinct but as yet undefined recep tor. Here, we demonstrate that some FeLV-Bs can also use human Pit2 (H uPit2) and hamster Pit2 (HaPit2) for entry. By making viruses that con tain chimeric surface (SU) envelope proteins from FeLV-A and FeLV-B, a nd testing their infectivity, we have defined genetic determinants tha t confer host range and specific receptor recognition, HuPit1 receptor recognition determinants localize to the N-terminal region of the FeL V-B SU, amino acids 83 to 116, encompassing the N-terminal portion of variable region A (VRA), While this 34-amino-acid domain of the FeLV-B VRA is sufficient for infection of some cells (feline, canine,and hum an), amino acids 146 to 249 of FeLV-B, which include variable region B (VRB), were required for efficient infection in other cell types (ham ster, bovine, and rat), Chimeras encoding FeLV-B VRA and VRB also infe cted cells expressing HaPit2 and HuPit2 receptors more efficiently tha n chimeras encoding only the VRA of FeLV-B, suggesting that VRB provid es a secondary determinant that is both cell and receptor specific, Ho wever, viruses containing additional FeLV-B sequences in the C terminu s of SU could not recognize HuPit2, implying that there is a determina nt beyond VRB that negatively affects HuPit2 interactions, Thus, Pit2 recognition may drive selection for the generation of specific FeLV-B recombinants, offering an explanation for the two major classes of FeL V-B that have been observed in vivo. Furthermore, the finding that som e FeLV-Bs can use both Pit1 and Pit2 may explain previous observations that FeLV-B and GALV, which primarily uses Pit1, display nonreciproca l interference on many cell types.