IDENTIFICATION AND CHARACTERIZATION OF THE VIRAL INTERACTION DETERMINANT OF THE SUBGROUP-A AVIAN-LEUKOSIS VIRUS RECEPTOR

The cellular receptor for subgroup A avian leukosis viruses (ALV-A) ha s a small, 83-amino-acid extracellular domain containing a motif that is related in sequence to the ligand binding repeats of the low-densit y lipoprotein receptor, Extensive mutagenesis of the ALV-A receptor ha s identified two acidic amino acids (Asp-46 and Glu-47) and an adjacen t aromatic amino acid (Trp-48) in the carboxy-terminal portion of this low density lipoprotein receptor-related motif that are crucial for e fficient viral entry. In addition, a 19-amino-acid peptide derived fro m this region efficiently and specifically blocked subgroup A viral in fection when oxidized to form a disulfide bond previously predicted to form in the native receptor (C. Belanger, K. Zingler, and J. A. T. Yo ung, J. Virol. 69:1019-1024, 1995). Thus, the charged and aromatic ami no acid determinants that are required for viral infection appear to l ie on a small loop region of the ALV-A receptor. Previously, a single aromatic and one or more charged residues on the CD4 receptor for huma n and simian immunodeficiency viruses, and the MCAT receptor for ecotr opic murine leukemia viruses, were shown to be important for viral ent ry. These results suggest that different retroviruses may recognize re lated determinants on structurally divergent cellular receptors.