Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic, and polytropic murine leukemia viruses.
The envelope glycoproteins (SU) of mammalian type C retroviruses possess an amino-terminal domain of about 200 residues, which is involved in binding a cell surface receptor. In this domain, highly conserved amino acid sequences are interrupted by two segments of variable length and sequence, VRA and VRB. We have studied the role of these variable regions in receptor recognition and binding by constructing chimeric molecules in which portions of the amino-terminal domains from amphotropic (4070A), xenotropic (NZB), and polytropic (MCF 247) murine leukemia virus SU proteins were permuted. These chimeras, which exchanged either one or two variable regions, were expressed at the surface of replication-defective viral particles by a pseudotyping assay. Wild-type or recombinant env genes were transfected into a cell line producing Moloney murine leukemia virus particles devoid of envelope glycoproteins in which a retrovirus vector genome carrying an Escherichia coli lacZ gene was packaged. The host range and sensitivity to interference of pseudotyped virions were assayed, and we observed which permutations resulted in receptor switch or loss of function. Our results indicate that the determinants of receptor choice are found within the just 120 amino acids of SU proteins. Downstream sequences contribute to the stabilization of the receptor-specific structure.
Battini
J L
JL
Laboratoire Rétrovirus et Transfert Génétique, Institut Pasteur, Paris, France.
Heard
J M
JM
Danos
O
O
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D015686:Gene Products, env; D066298:In Vitro Techniques; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins; D015183:Restriction Mapping; D016415:Sequence Alignment; D013045:Species Specificity; D014162:Transfection; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D015686:Gene Products, env; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins