Dataset Information

Structural comparison of HIV-1 envelope spikes with and without the V1/V2 loop.

ABSTRACT: We have used cryoelectron tomography of vitreous-ice-embedded HIV-1 virions to compare the envelope (Env) spikes of a wild-type strain with those of a mutant strain in which the V1/V2 loop has been deleted. Deletion of V1/V2 results in a spike with far more structural heterogeneity than is observed in the wild type, likely reflecting greatly enhanced gp120 protomer flexibility. A major difference between the two forms is a pronounced loss of mass from the "peak" of the native Env spike. The apparent loss of contact among three gp120 protomers likely accounts for the more open structure, heterogeneity in configuration, and previous observations that broadly neutralizing epitopes and reactive sites on other structural elements are more exposed in such constructs.

SUBMITTER: Hu G

PROVIDER: S-EPMC3067966 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Structural comparison of HIV-1 envelope spikes with and without the V1/V2 loop.

Hu Guiqing G Liu Jun J Taylor Kenneth A KA Roux Kenneth H KH

Journal of virology 20101229 6

We have used cryoelectron tomography of vitreous-ice-embedded HIV-1 virions to compare the envelope (Env) spikes of a wild-type strain with those of a mutant strain in which the V1/V2 loop has been deleted. Deletion of V1/V2 results in a spike with far more structural heterogeneity than is observed in the wild type, likely reflecting greatly enhanced gp120 protomer flexibility. A major difference between the two forms is a pronounced loss of mass from the "peak" of the native Env spike. The appa ...[more]

PMID: 21191026

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Project description:Recent studies have described several broadly neutralizing monoclonal antibodies (bN-mAbs) that recognize glycan-dependent epitopes (GDEs) in the HIV-1 envelope protein, gp120. These were recovered from HIV-1 infected subjects, and several (e.g., PG9, PG16, CH01, CH03) target glycans in the first and second variable (V1/V2) domain of gp120. The V1/V2 domain is thought to play an important role in conformational masking, and antibodies to the V1/V2 domain were recently identified as the only immune response that correlated with protection in the RV144 HIV-1 vaccine trial. While the importance of antibodies to polymeric glycans is well established for vaccines targeting bacterial diseases, the importance of antibodies to glycans in vaccines targeting HIV has only recently been recognized. Antibodies to GDEs may be particularly significant in HIV vaccines based on gp120, where 50% of the molecular mass of the envelope protein is contributed by N-linked carbohydrate. However, few studies have reported antibodies to GDEs in humans or animals immunized with candidate HIV-1 vaccines. In this report, we describe the isolation of a mouse mAb, 4B6, after immunization with the extracellular domain of the HIV-1 envelope protein, gp140. Epitope mapping using glycopeptide fragments and in vitro mutagenesis showed that binding of this antibody depends on N-linked glycosylation at asparagine N130 (HXB2 numbering) in the gp120 V1/V2 domain. Our results demonstrate that, in addition to natural HIV-1 infection, immunization with recombinant proteins can elicit antibodies to the GDEs in the V1/V2 domain of gp120. Although little is known regarding conditions that favor antibody responses to GDEs, our studies demonstrate that these antibodies can arise from a short-term immunization regimen. Our results suggest that antibodies to GDEs are more common than previously suspected, and that further analysis of antibody responses to the HIV-1 envelope protein will lead to the discovery of additional antibodies to GDEs.

Dataset Information

Structural comparison of HIV-1 envelope spikes with and without the V1/V2 loop.

Publications

Structural comparison of HIV-1 envelope spikes with and without the V1/V2 loop.

Similar Datasets

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