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) has a small, 83-amino-acid extracellular domain containing a motif that is related in sequence to the ligand binding repeats of the low-density lipoprotein receptor. Extensive mutagenesis of the ALV-A receptor has identified two acidic amino acids (Asp-46 and Glu-47) and an adjacent aromatic amino acid (Trp-48) in the carboxy-terminal portion of this low-density lipoprotein receptor-related motif that are crucial for efficient viral entry. In addition, a 19-amino-acid peptide derived from this region efficiently and specifically blocked subgroup A viral infection when oxidized to form a disulfide bond previously predicted to form in the native receptor (C. Bélanger, K. Zingler, and J. A. T. Young, J. Virol. 69:1019-1024, 1995). Thus, the charged and aromatic amino acid determinants that are required for viral infection appear to lie 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 human and simian immunodeficiency viruses, and the MCAT receptor for ecotropic murine leukemia viruses, were shown to be important for viral entry. These results suggest that different retroviruses may recognize related determinants on structurally divergent cellular receptors.
Zingler
K
K
Gladstone Institute of Virology and Immunology, University of California School of Medicine, San Francisco 94141-9100, USA.
Bélanger
C a
Ca
Peters
R
R
Agard
E
E
Young
J A
JA
D001355:Alpharetrovirus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology*; D013329:Structure-Activity Relationship
D015704:CD4 Antigens; D010446:Peptide Fragments; D011991:Receptors, Virus