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Hypervariable region 3 residues of HIV type 1 gp120 involved in CCR5 coreceptor utilization: therapeutic and prophylactic implications.
Wang WK; Dudek T; Essex M; Lee TH; Department of Immunology and
July 30, 1999
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4558-62. Unique Identifier :

Crystallographic characterization of a ternary complex containing a monomeric gp120 core, parts of CD4, and a mAb, revealed a region that bridges the inner and outer domains of gp120. In a related genetic study, several residues conserved among primate lentiviruses were found to play important roles in CC-chemokine receptor 5 (CCR5) coreceptor utilization, and all but one were mapped to the bridging domain. To reconcile this finding with previous reports that the hypervariable region 3 (V3) of gp120 plays an important role in chemokine coreceptor utilization, elucidating the roles of various V3 residues in this critical part of the HIV type 1 (HIV-1) life cycle is essential. Alanine-scanning mutagenesis was carried out to identify V3 residues critical for CCR5 utilization. Our findings demonstrated that several residues in V3 were critical to CCR5 utilization. Furthermore, these residues included not only those conserved across HIV-1 subtypes, but also those that varied among HIV-1 subtypes. Although the highly conserved V3 residues may represent unique targets for antiviral designs, the involvement of variable residues raises the possibility that antigenic variation in the coreceptor binding domain could further complicate HIV-1 vaccine design.

JOURNAL ARTICLE Alanine Amino Acid Sequence Amino Acid Substitution Binding Sites Cell Line Consensus Sequence CD4-Positive T-Lymphocytes/IMMUNOLOGY/VIROLOGY Human HIV Envelope Protein gp120/*CHEMISTRY/GENETICS/*METABOLISM HIV-1/GENETICS/*PHYSIOLOGY Immunoglobulins, Fab/CHEMISTRY Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Protein Structure Receptors, CCR5/CHEMISTRY/*PHYSIOLOGY Sequence Alignment Sequence Homology, Amino Acid Support, U.S. Gov't, P.H.S. Variation (Genetics)