title: Length polymorphism within the second variable region of the human immunodeficiency virus type 1 envelope glycoprotein affects accessibility of the receptor binding site.
abstract: Sequential mutations were introduced into the V2 region of human immunodeficiency virus (HIV) type 1 HXB2, affecting the length, charge, and number of potential glycosylation sites. The insertions had no effect on cytopathicity or on the ability of virus to replicate in peripheral blood mononuclear cells and established T-cell lines. However, deletion of amino acids 186 to 188, encoding a conserved glycosylation site, resulted in a nonviable virus, suggesting a minimal length requirement of 40 amino acids for a functional V2 loop. However, all amino acid insertions affected the sensitivity of the variants to neutralization by soluble CD4 and monoclonal antibodies specific for epitopes in the V3 and CD4 binding site regions. Furthermore, these mutant viruses showed resistance to neutralization by HIV-positive human sera. Soluble gp120 mutant glycoproteins showed increased affinities for soluble CD4 and monoclonal antibodies specific for a number of epitopes overlapping the CD4 binding site, confirming that length increases in V2 affect exposure of the CD4 binding site. In summary, these data demonstrate that differences in V2 length modulate immunoreactivity of the envelope glycoprotein and support an association between the V2 and CD4 binding site regions.
authors.affiliation: University of Reading, School of Animal and Microbial Sciences, Whiteknights, United Kingdom.
authors.forename: D G
authors.initials: DG
authors.lastname: Fox
authors.forename: P
authors.initials: P
authors.lastname: Balfe
authors.forename: C P
authors.initials: CP
authors.lastname: Palmer
authors.forename: J C
authors.initials: JC
authors.lastname: May
authors.forename: C
authors.initials: C
authors.lastname: Arnold
authors.forename: J A
authors.initials: JA
authors.lastname: McKeating
mesh_terms: D001665:Binding Sites; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009500:Neutralization Tests; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus