Structure of a V3-containing HIV-1 gp120 core

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Science (Impact Factor: 33.61). 12/2005; 310(5750):1025-8. DOI: 10.1126/science.1118398
Source: PubMed


The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization.


Available from: Richard Wyatt
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    • "However, the enhanced reactivity by sCD4 was observed against Env on the cell surface in most of anti- V3 MAbs (Fig. 2). This is consistent with the previous reports (Huang et al., 2005; Thali et al., 1993), which showed that the binding of CD4 to gp120 caused the V3 to protrude and became more available, particularly in the strains that use the CCR5 coreceptor . Although a reduction of reactivity was observed for the CD4bs MAbs in ELISA, this reduction of reactivity against trimeric Env was not obvious in the MAbs, such as 4E3 and 49G2 (Fig. 2). "
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    ABSTRACT: Antibodies with modest neutralizing activity and narrow breadth are commonly elicited in HIV-1. Here, we evaluated the complementary and synergistic activities of a set of monoclonal antibodies (MAb) isolated from a single patient, directed to V3, CD4 binding site (CD4bs), and CD4 induced (CD4i) epitopes. Despite low somatic hypermutation percentages in the variable regions, these MAbs covered viral strains from subtypes B, C, A and CRF01_AE and transmitted/founder viruses in terms of binding, neutralizing and antibody-dependent cell-mediated cytotoxicity (ADCC) activities. In addition, a combination of the anti-V3 and CD4bs MAbs showed a synergistic effect over the neutralization of HIV-1JR-FL. A humoral response from a single patient covered a wide range of viruses by complementary and synergistic activities of antibodies with different specificities. Inducing a set of narrow neutralizing antibodies, easier to induce than the broadly neutralizing antibodies, could be a strategy for developing an effective vaccine against HIV-1. Copyright © 2014 Elsevier Inc. All rights reserved.
    Virology 12/2014; 475C:187-203. DOI:10.1016/j.virol.2014.11.011 · 3.32 Impact Factor
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