title: Mapping of equine lentivirus receptor 1 residues critical for equine infectious anemia virus envelope binding.
abstract: The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complementary exchanges of the respective cysteine-rich domains (CRD) between the ELR1 and murine HveA proteins revealed CRD1 as the predominant determinant of functional gp90 binding to ELR1 and also to a chimeric murine HveA protein expressed on the surface of transfected Cf2Th cells. Mutations of individual amino acids in the CRD1 segment of ELR1 and murine HveA indicated the Leu70 in CRD1 as essential for functional binding of EIAV gp90 and for virus infection of transduced Cf2Th cells. The specificity of the EIAV SU binding domain identified for the ELR1 receptor is fundamentally identical to that reported previously for functional binding of feline immunodeficiency virus SU to its coreceptor CD134, another TNFR protein. These results indicate unexpected common features of the specific mechanisms by which diverse lentiviruses can employ TNFR proteins as functional receptors.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1144 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Zhang
authors.forename: Chengqun
authors.initials: C
authors.lastname: Sun
authors.forename: Sha
authors.initials: S
authors.lastname: Jin
authors.forename: Michael
authors.initials: M
authors.lastname: Cascio
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004285:Dogs; D006023:Glycoproteins / Q000378:metabolism*; D004860:Infectious Anemia Virus, Equine / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D006023:Glycoproteins; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C091940:SU protein, equine infectious anemia virus; D014759:Viral Envelope Proteins