title: Distinctive receptor binding properties of the surface glycoprotein of a natural feline leukemia virus isolate with unusual disease spectrum.
abstract: BACKGROUND
  Feline leukemia virus (FeLV)-945, a member of the FeLV-A subgroup, was previously isolated from a cohort of naturally infected cats. An unusual multicentric lymphoma of non-T-cell origin was observed in natural and experimental infection with FeLV-945. Previous studies implicated the FeLV-945 surface glycoprotein (SU) as a determinant of disease outcome by an as yet unknown mechanism. The present studies demonstrate that FeLV-945 SU confers distinctive properties of binding to the cell surface receptor.
  
  
  RESULTS
  Virions bearing the FeLV-945 Env protein were observed to bind the cell surface receptor with significantly increased efficiency, as was soluble FeLV-945 SU protein, as compared to the corresponding virions or soluble protein from a prototype FeLV-A isolate. SU proteins cloned from other cohort isolates exhibited increased binding efficiency comparable to or greater than FeLV-945 SU. Mutational analysis implicated a domain containing variable region B (VRB) to be the major determinant of increased receptor binding, and identified a single residue, valine 186, to be responsible for the effect.
  
  
  CONCLUSIONS
  The FeLV-945 SU protein binds its cell surface receptor, feTHTR1, with significantly greater efficiency than does that of prototype FeLV-A (FeLV-A/61E) when present on the surface of virus particles or in soluble form, demonstrating a 2-fold difference in the relative dissociation constant. The results implicate a single residue, valine 186, as the major determinant of increased binding affinity. Computational modeling suggests a molecular mechanism by which residue 186 interacts with the receptor-binding domain through residue glutamine 110 to effect increased binding affinity. Through its increased receptor binding affinity, FeLV-945 SU might function in pathogenesis by increasing the rate of virus entry and spread in vivo, or by facilitating entry into a novel target cell with a low receptor density.
authors.affiliation: Department of Microbiology and Immunology and Tulane Cancer Center, Tulane University School of Medicine, 1430 Tulane Avenue SL-38, New Orleans, LA 70112, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Bolin
authors.forename: Chandtip
authors.initials: C
authors.lastname: Chandhasin
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Lobelle-Rich
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Albritton
authors.forename: Laura S
authors.initials: LS
authors.lastname: Levy
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002415:Cats; D002460:Cell Line; D005256:Leukemia Virus, Feline / Q000472:pathogenicity*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism*; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism*; D014633:Valine / Q000235:genetics; D014759:Viral Envelope Proteins / Q000378:metabolism*; D056189:Viral Tropism; D053585:Virus Attachment
chemical_list: D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; C074548:feline leukemia virus receptor; C073723:glycoprotein gp70, Feline leukemia virus; D014633:Valine