title: Association of structural changes in the V2 and V3 loops of the gp120 envelope glycoprotein with acquisition of neutralization resistance in a simian-human immunodeficiency virus passaged in vivo.
abstract: The in vivo passage of a neutralization-sensitive, laboratory-adapted simian-human immunodeficiency virus (SHIV-HXBc2) generated a pathogenic, neutralization-resistant virus, SHIV-HXBc2P 3.2. SHIV-HXBc2P 3.2 differs from SHIV-HXBc2 only in 13 amino acid residues of the viral envelope glycoproteins. Here we used antibody competition analysis to examine the structural changes that occurred in the SHIV-HXBc2P 3.2 gp120 exterior envelope glycoprotein. The relationships among the antibody epitopes on the conserved gp120 core of SHIV-HXBc2 and SHIV-HXBc2P 3.2 were similar. The third variable (V3) loop was more closely associated with the fourth conserved (C4) region and CD4-induced epitopes on the gp120 core in the HXBc2P 3.2 gp120 glycoprotein compared with the HXBc2 gp120 glycoprotein. Rearrangements of the second variable (V2) loop with respect to the CD4 binding site and associated epitopes were evident in comparisons of the two gp120 glycoproteins. Thus, the in vivo evolution of a neutralization-resistant virus involves conformational adjustments of the V2 and V3 variable loops with respect to the conserved receptor-binding regions of the gp120 core.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ye
authors.forename: Z H
authors.initials: ZH
authors.lastname: Si
authors.forename: J P
authors.initials: JP
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000818:Animals; D001665:Binding Sites; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D011487:Protein Conformation; D016865:Reassortant Viruses / Q000737:chemistry / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000502:physiology*; D014779:Virus Replication
chemical_list: D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus