Characterization of determinants for envelope binding and infection in tva, the subgroup A avian sarcoma and leukosis virus receptor.
Tva is the cellular receptor for subgroup A avian leukosis and sarcoma virus (ALSV-A). The viral interaction domain of Tva is determined by a 40-residue, cysteine-rich module closely related to the ligand binding domain of the human low-density lipoprotein receptor (LDLR). In this report, we examined the role of the LDLR-like module of Tva in envelope binding and viral infection by mutational analysis. We found that the entire LDLR module in Tva is essential for efficient binding to the viral envelope protein. However, the 17 N-terminal residues of this module can be deleted without affecting receptor function, suggesting that the major determinants for viral entry are located at the C terminus of the module. The effect on viral infection of many amino acid substitutions and deletions in the LDLR module is context dependent, suggesting that the residues important for viral entry are dispersed throughout the LDLR module. In addition, we found that all 27 mutations at residues D46, E47, and W48 greatly reduced envelope binding. These results are discussed in relation to a recently elucidated structure for an LDLR module.
Rong
L
L
Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Gendron
K
K
Strohl
B
B
Shenoy
R
R
Wool-Lewis
R J
RJ
Bates
P
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001354:Avian Leukosis Virus / Q000502:physiology*; D030161:Avian Proteins; D001358:Avian Sarcoma Viruses / Q000502:physiology*; D001665:Binding Sites; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D006801:Humans; D008969:Molecular Sequence Data; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
D030161:Avian Proteins; D011973:Receptors, LDL; D011991:Receptors, Virus; C088745:Tva receptor; D014759:Viral Envelope Proteins