title: Variable regions A and B in the envelope glycoproteins of feline leukemia virus subgroup B and amphotropic murine leukemia virus interact with discrete receptor domains.
abstract: The surface (SU) envelope glycoproteins of feline leukemia virus subgroup B (FeLV-B) and amphotropic murine leukemia virus (A-MLV) are highly related, even in the variable regions VRA and VRB that have been shown to be required for receptor recognition. However, FeLV-B and A-MLV use different sodium-dependent phosphate symporters, Pit1 and Pit2, respectively, as receptors for infection. Pit1 and Pit2 are predicted to have 10 membrane-spanning domains and five extracellular loops. The close relationship of the retroviral envelopes enabled us to generate pseudotype virions carrying chimeric FeLV-B/A-MLV envelope glycoproteins. We found that some of the pseudotype viruses could not use Pit1 or Pit2 proteins but could efficiently utilize specific chimeric Pit1/Pit2 proteins as receptors. By studying Mus dunni tail fibroblasts expressing chimeric Pit1/Pit2 proteins and pseudotype virions carrying chimeric FeLV-B/A-MLV envelopes, we show that FeLV-B and A-MLV VRA and VRB interact in a modular manner with specific receptor domains. Our results suggest that FeLV-B VRA interacts with Pit1 extracellular loops 4 and 5 and that residues Phe-60 and Pro-61 of FeLV-B VRA are essential for receptor choice. However, this interaction is insufficient for infection, and an additional interaction between FeLV-B VRB and Pit1 loop 2 is essential. Similarly, A-MLV infection requires interaction of A-MLV VRA with Pit2 loops 4 and 5 and VRB with Pit2 loop 2, with residues Tyr-60 and Val-61 of A-MLV VRA being critical for receptor recognition. Together, our results suggest that FeLV-B and A-MLV infections require two major discrete interactions between the viral SU envelope glycoproteins and their respective receptors. We propose a common two-step mechanism for interaction between retroviral envelope glycoproteins and cell surface receptors.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA. tailorc@ohsu.edu
authors.forename: C S
authors.initials: CS
authors.lastname: Tailor
authors.forename: D
authors.initials: D
authors.lastname: Kabat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005256:Leukemia Virus, Feline / Q000378:metabolism*; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D013329:Structure-Activity Relationship; D027981:Symporters; D014443:Tyrosine / Q000378:metabolism; D014633:Valine / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D014759:Viral Envelope Proteins; C073723:glycoprotein gp70, Feline leukemia virus; D014443:Tyrosine; D010649:Phenylalanine; D011392:Proline; D014633:Valine