Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic, and polytropic murine leukemia viruses

Abstract

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.

Differential Inhibition of Retrovirus Transduction by Proteoglycans and Free Glycosaminoglycans

“…The amino acid positions were numbered sequentially, beginning with the first residue of the mature SU protein. Variable regions were as defined in Battini et al (10). b Amino acids 129 and 130 are in VRB.…”

“…Binding and fusion are mediated by a specific interaction between the envelope protein of the virus (SU) and its receptor, and their interaction is absolutely required for successful transduction (6,7). As a result, most research efforts to better understand early virus-cell interactions have focused on the envelopereceptor interaction (8)(9)(10)(11).…”

Differential Inhibitory Effects of Cyanovirin-N, Griffithsin, and Scytovirin on Entry Mediated by Envelopes of Gammaretroviruses and Deltaretroviruses

“…These differences suggest that the susceptibility of the gammaretroviruses to CV-N reflects the ability of this lectin to bind at one or more of these glycosylation sites. Sites 1 and 2 lie within the gammaretroviral receptor binding domain region (RBD) (34,35) within close proximity to residues previously identified as critical for Env function. Site 1 is 4 residues downstream of a histidine residue within the motif PHQ, which has been shown to be critical for fusion of gammaretroviruses to their target cells (36)(37)(38).…”

Pathogenicity of a Mutant Friend Spleen Focus‐Forming Virus Encoding an Env‐Like Membrane Glycoprotein (gp55) with Substitution by a Xenotropic Murine Leukemia Virus Env gp70 Sequence

“…MuLVs are grouped into 5 classes according to their infection host range properties; namely, ecotropic, xenotropic, amphotropic, polytropic, and a class represented by the 10A1 MuLV. Infection host range properties of MuLVs are primarily determined by the specific interaction between the amino-terminal region of the Env gp70 subunit and a receptor protein on the target cell surface (3,4,6). Gp55 has an MCF MuLV Env gp70 amino-terminal region, and there is evidence (12) showing that gp55 binds to an MCF MuLV receptor protein in the F-SFFV-infected fibroblast cells of a laboratory strain mouse.…”

“…In this study, in order to clarify the role of the presumed binding of gp55 to the MCF MuLV receptor protein for pathogenicity, we analyzed the biological activities both in vivo and in vitro of a constructed mutant gp55 which has a xenotropic (XE) MuLV gp70 aminoterminal region, whose sequence is almost identical to that of the MCF MuLV gp70 except for a portion of the sequence responsible for binding to the MCF MuLV receptor protein (4,16).…”