Single-round selection yields a unique retroviral envelope utilizing GPR172A as its host receptor.
The recognition by a viral envelope of its cognate host-cell receptor is the initial critical step in defining the viral host-range and tissue specificity. This study combines a single-round of selection of a random envelope library with a parallel cDNA screen for receptor function to identify a distinct retroviral envelope/receptor pair. The 11-aa targeting domain of the modified feline leukemia virus envelope consists of a constrained peptide. Critical to the binding of the constrained peptide envelope to its cellular receptor are a pair of internal cysteines and an essential Trp required for maintenance of titers >10(5) lacZ staining units per milliliter. The receptor used for viral entry is the human GPR172A protein, a G-protein-coupled receptor isolated from osteosarcoma cells. The ability to generate unique envelopes capable of using tissue- or disease-specific receptors marks an advance in the development of efficient gene-therapy vectors.
Mazari
Peter M
PM
University of Medicine and Dentistry of New Jersey-The Robert Wood Johnson Medical School, Department of Biochemistry, Piscataway, NJ 08854, USA.
Linder-Basso
Daniela
D
Sarangi
Anindita
A
Chang
Yehchung
Y
Roth
Monica J
MJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D005256:Leukemia Virus, Feline / Q000737:chemistry*; D012516:Osteosarcoma / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry*
D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; C540350:SLC52A2 protein, human; D014759:Viral Envelope Proteins