title: Role of basic residues in the subgroup-determining region of the subgroup A avian sarcoma and leukosis virus envelope in receptor binding and infection.
abstract: Receptor specificity in avian sarcoma and leukosis viruses (ASLV) maps to the central region of the envelope surface protein, SU. Two hypervariable regions, hr1 and hr2, within this region of SU are the principal determinants of receptor specificity. The cellular receptor for subgroup A ASLV, Tva, utilizes a 40-residue, acidic, cysteine-rich sequence for viral binding and entry. This domain in Tva is closely related to the ligand-binding domain of the low-density lipoprotein receptor (LDLR). Ligands bind to LDLR via the interaction of clustered basic residues in the ligand with the acidic cysteine-rich domains of the receptor. Analysis of the ASLV envelope sequences revealed a cluster of basic residues within hr2 that is unique to the subgroup A viruses, suggesting a possible role for these residues in receptor recognition. Therefore, the effects of altering these basic residues on subgroup A envelope expression, receptor binding, and infectivity were examined. Most of the mutant proteins were transported to the cell surface and processed normally. Receptor binding was diminished approximately 50% by alanine substitution at amino acid R213 or K227, whereas substitution by alanine at R210, R223, or R224 had no effect. However, when coupled with mutations at R213 or K227, changes at R223,R224 reduced envelope binding by 90%. Mutation of all five basic residues abrogated receptor binding. The effect of the hr2 mutations on ASLV envelope-mediated infection did not parallel the effect on receptor binding. Residues 210, 213, 223, and 224 were important for efficient infection, while mutations at residue 227 had little effect on infectivity. These results demonstrate that the basic residues in the ASLV envelope have roles in both receptor recognition and post-receptor binding events during viral entry.
authors.affiliation: Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rong
authors.forename: A
authors.initials: A
authors.lastname: Edinger
authors.forename: P
authors.initials: P
authors.lastname: Bates
mesh_terms: D001355:Alpharetrovirus / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D009154:Mutation; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000502:physiology
chemical_list: D011991:Receptors, Virus; D014759:Viral Envelope Proteins