title: An immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 (HXB2-Env:Ala 582(-->Thr)) decreases viral neutralization by monoclonal antibodies to the CD4-binding site.
abstract: An immune-selected point-mutation (HXB2-Env:Ala582(-->Thr)) in the transmembrane protein, gp41, of the human immunodeficiency virus type 1 confers relative insensitivity to neutralization by a number of sera from HIV-1-positive persons. Affinity-purified human antibodies to continuous epitopes spanning Ala582 do not neutralize the virus (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. J. Robert-Guroff, J. Virol. 64, 3240-3248, 1990). The specificity of the antibodies that the mutation renders less active has not previously been determined. We now report that this substitution in gp41 reduces the neutralizing activity of monoclonal antibodies to discontinuous gp120 epitopes, which overlap with the CD4-binding site. There was no such difference in sensitivity to neutralization by soluble CD4, CD4-immunoglobulin, or by two monoclonal antibodies to the V3 region of gp120. Furthermore, the ability of 10 human HIV-1-positive sera to block the binding of soluble CD4 to mammalian-recombinant gp120 correlated weakly with their differentiation of neutralization between the wild-type and the Env:Ala582(-->Thr)-mutant virus. We thus suggest that the substitution in gp41 modulates the conformation of gp120 so as to decrease viral sensitivity to one category of antibodies which is partly responsible for the group-specific neutralization of HIV-1 by human sera.
authors.affiliation: Institute of Medical Microbiology, Lund University, Sweden.
authors.forename: P J
authors.initials: PJ
authors.lastname: Klasse
authors.forename: J A
authors.initials: JA
authors.lastname: McKeating
authors.forename: M
authors.initials: M
authors.lastname: Schutten
authors.forename: M S
authors.initials: MS
authors.lastname: Reitz
authors.forename: M
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017354:Point Mutation
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41