ArticleJournal of virology2017
Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
- Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency.Journal of virology · 2020Trial
- Charting the Path Forward for HIV Immune-Based Prevention: Contributions of the Division of AIDS at NIAID.Vaccines · 2026Article
- Conformational dynamics of the HIV-1 envelope glycoprotein from CRF01_AE is associated with susceptibility to antibody-dependent cellular cytotoxicity.Journal of virology · 2026Article
- A gp41 HR2 residue modulates the susceptibility of HIV-1 envelope glycoproteins to small molecule inhibitors targeting gp120.Journal of virology · 2025Article
- The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.Journal of virology · 2024Article
- The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.bioRxiv : the preprint server for biology · 2024Article
- Implications of the 375W mutation for HIV-1 tropism and vaccine development.Journal of virology · 2024Article
- Structure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir.Nature communications · 2023Article
- Article
- Temsavir blocks the immunomodulatory activities of HIV-1 soluble gp120.Cell chemical biology · 2023Article
- Temsavir Modulates HIV-1 Envelope Conformation by Decreasing Its Proteolytic Cleavage.Viruses · 2023Article
- Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.Journal of virology · 2023Article
- Article
- Small CD4 mimetics sensitize HIV-1-infected macrophages to antibody-dependent cellular cytotoxicity.Cell reports · 2023Article
- HIV-1 Vpu restricts Fc-mediated effector functions in vivo.Cell reports · 2022Article
- Antibody-dependent cellular cytotoxicity responses and susceptibility influence HIV-1 mother-to-child transmission.JCI insight · 2022Article
- Detection of the HIV-1 Accessory Proteins Nef and Vpu by Flow Cytometry Represents a New Tool to Study Their Functional Interplay within a Single Infected CD4Journal of virology · 2022Article
- Selection of HIV Envelope Strains for Standardized Assessments of Vaccine-Elicited Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies.Journal of virology · 2022Article
- Article
- Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir.Cell host & microbe · 2021Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
Abstract
HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid the exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to the CD4-bound state. While residue S375 is well conserved in the majority of group M HIV-1 isolates, CRF01_AE strains have a naturally occurring histidine at this position (H375). Interestingly, CRF01_AE is the predominant circulating strain in Thailand, where the RV144 trial took place. In this trial, which resulted in a modest degree of protection, ADCC responses were identified as being part of the correlate of protection. Here we investigate the influence of the Phe 43 cavity on ADCC responses. Filling this cavity with a histidine or tryptophan residue in Env with a natural serine residue at this position (S375H/W) increased the susceptibility of HIV-1-infected cells to ADCC. Conversely, the replacement of His 375 by a serine residue (H375S) within HIV-1 CRF01_AE decreased the efficiency of the ADCC response. Our results raise the intriguing possibility that the presence of His 375 in the circulating strain where the RV144 trial was held contributed to the observed vaccine efficacy.
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