Three 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 FeLV (FeLV-A) by recombining with portions of endogenous FeLV envelope sequences in the cat genome. The replication properties of FeLV-B are distinct from those of FeLV-A; FeLV-B infects many nonfeline cell lines and recognizes the human Pit1 (HuPit1) receptor, whereas FeLV-A infects primarily feline cells, using a distinct but as yet undefined receptor. Here, we demonstrate that some FeLV-Bs can also use human Pit2 (HuPit2) and hamster Pit2 (HaPit2) for entry. By making viruses that contain chimeric surface (SU) envelope proteins from FeLV-A and FeLV-B, and testing their infectivity, we have defined genetic determinants that confer host range and specific receptor recognition. HuPit1 receptor recognition determinants localize to the N-terminal region of the FeLV-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 human), amino acids 146 to 249 of FeLV-B, which include variable region B (VRB), were required for efficient infection in other cell types (hamster, bovine, and rat). Chimeras encoding FeLV-B VRA and VRB also infected cells expressing HaPit2 and HuPit2 receptors more efficiently than chimeras encoding only the VRA of FeLV-B, suggesting that VRB provides a secondary determinant that is both cell and receptor specific. However, viruses containing additional FeLV-B sequences in the C terminus of SU could not recognize HuPit2, implying that there is a determinant 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 FeLV-B that have been observed in vivo. Furthermore, the finding that some FeLV-Bs can use both Pit1 and Pit2 may explain previous observations that FeLV-B and GALV, which primarily uses Pit1, display nonreciprocal interference on many cell types.
Boomer
S
S
University of Washington, Seattle 98195, USA.
Eiden
M
M
Burns
C C
CC
Overbaugh
J
J
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002415:Cats / Q000821:virology; D002417:Cattle; D002478:Cells, Cultured; D006224:Cricetinae; D004285:Dogs; D006801:Humans; D005256:Leukemia Virus, Feline / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011991:Receptors, Virus / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C070506:ecotropic murine leukemia virus receptor; C067981:leukemia virus receptor, gibbon ape