Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Abstract

Infection of target host cells by the human immunodeficiency virus-1 (HIV-1) is a multi-step process involving a series of conformational changes in the viral gp120 and gp41 proteins. Gp120 binding to the main cell receptor, CD4, on the surface of cells expressing this molecule, and interaction with the cell chemokine receptors CCR5 and CXCR4, are among the key events for HIV-1 infection. These steps are crucial for the virus and offer potential therapeutic targets. For this reason, understanding the structure and the physicochemical characteristics of the gp120 in relation to these interactions has drawn much attention. This review article focuses on the biologically important V3 region of the gp120 and summarizes the functional role, the sequence variation and the conformational features of V3 peptides, which are important for co-receptor selectivity, specificity and interaction. Synthetic V3 peptides have been extensively studied by NMR spectroscopy and X-ray crystallography, in solution or in solid state, in their free or bound form, and valuable information was generated with the aim to be exploited in the design of new, effective inhibitors of HIV-1 infection. The features of the potential gp120 interacting sites on the two chemokine co-receptors, CCR5 and CXCR4, are also discussed, and co-receptor blocking molecules under clinical trial are also reported.

Subtype B Was the Dominant Strain Among HIV Type 1 Infections Except for the Population of Men Who Have Sex with Men in Harbin City, China

“…V3 in different HIV-1 subtypes has distinct antigenic properties. 10,11 In this study, the main tetramers on the tip of the V3 loop in CRF01_AE and CRF07_BC were GPGQ (15/22) and (6/6), respectively (Fig. 2), whereas the tetramer in CRF07_BC was the most conservative in our study.…”

“…10 V3 of env is a cysteine-bound loop structurally composed of 35 amino acids, with the principal neutralizing antibody determinant (PND) located in the crown of the V3 loop, 10,11 which is constituted of the specific tetramer (which locates the position of 15-18 of the V3 amino acid sequence). V3 in different HIV-1 subtypes has distinct antigenic properties.…”

“…V3 has long been a target of interest for entrybased inhibitors because of its critical role in defining the specificity of the interaction of env with cellular coreceptor molecules, usually CCR5 or CXCR4, to facilitate entry into target cells. 10,11 Our study has indicated that the tetramer on the crown of the V3 loop has greater diversity, especially for subtype B, compared with a previous study conducted in Harbin City published in 2007, which reported that 52.63% of the V3 tip amino motif was GPGQ and 21.53% was GPGR among 19 HIV-1-seropositive infectors that were identified with subtype B¢. 12 Moreover, the impact of the peculiar GWGR on the tip of the V3 loop among the B subtypes is worth noting for the development of profiles of HIV pathogenesis and vaccine design.…”

HIV-1 gp120/V3-derived epitopes promote activation-induced cell death to superantigen-stimulated CD4+/CD45RO+ T cells

“…We had shown previously with peptide-peptide V3-CCR5 interactions [21] that the amino terminal domain of CCR5 interacted with the V3 domain [34,35]. Using lipoV3-liposomes with five positive amino acid residues (LAI V3), we performed inhibition experiments with soluble V3 peptide derivatives that contained one (V3 +1 ) or nine (V3 +9 ) positively charged amino acids.…”

Crystal Structures of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralizing Antibody 2219 in Complex with Three Different V3 Peptides Reveal a New Binding Mode for HIV-1 Cross-Reactivity

“…The three peptides bound to Fab 2219 (19,23, and 23 amino acids long for the MN, UR29, and UG1033 peptides, respectively) all exhibit good electron density for 16 residues (Fig. 4), with all peptides forming a ␤-hairpin with a type II ␤-turn around residues P312 to P315.…”