Receptor-binding domain of murine leukemia virus envelope glycoproteins.
The surface glycoprotein (SU) of murine leukemia viruses (MuLVs) comprises two domains connected by a proline-rich hinge. The interaction of MuLV particles with subgroup-specific cell surface receptors depends primarily on two variable regions (VRA and VRB) located in the amino-terminal domain. To delineate the minimal receptor-binding domains, we examined the capacity of soluble envelope fragments to compete with the entry of virus particles. Amphotropic, ecotropic, polytropic, and xenotropic truncated SUs were produced by inserting stop codons in the env gene of the 4070A, Friend, MCF247 and NZB MuLVs, respectively. These fragments, as well as full-length envelope glycoproteins, were stably expressed in cells bearing the corresponding receptor. Synthesis, posttranslational modifications, transport, and secretion of the env gene products were monitored by immunoprecipitation. Cells expressing the modified SUs or naive cells preincubated with SU-containing conditioned media were infected with different pseudotypes of a retroviral vector carrying a beta-galactosidase marker gene. Reduction of cell susceptibility to infection in the presence of SU was used as a measure of receptor occupancy. The results indicated that the amphotropic and ecotropic envelope amino-terminal domains contain all of the determinants required for receptor binding. In contrast, additional sequences in the proline-rich region were needed for efficient interaction of the polytropic and xenotropic amino-terminal domains with the receptors.
Battini
J L
JL
Laboratoire Rétrovirus et Transfert Génétique, CNRS URA 1157, Institut Pasteur, Paris, France.
Danos
O
O
Heard
J M
JM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011392:Proline; D011991:Receptors, Virus / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014762:Viral Interference
D006023:Glycoproteins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D011392:Proline