ArticlemBio2021
Functional Anatomy of the Trimer Apex Reveals Key Hydrophobic Constraints That Maintain the HIV-1 Envelope Spike in a Closed State.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- V3 tip determinants of susceptibility to inhibition by CD4-mimetic compounds in natural clade A human immunodeficiency virus (HIV-1) envelope glycoproteins.Journal of virology · 2023Article
- Impact of stabilizing mutations on the antigenic profile and glycosylation of membrane-expressed HIV-1 envelope glycoprotein.PLoS pathogens · 2023Article
- Subtle Longitudinal Alterations in Env Sequence Potentiate Differences in Sensitivity to Broadly Neutralizing Antibodies following Acute HIV-1 Subtype C Infection.Journal of virology · 2022Article
- Regulation of epitope exposure in the gp41 membrane-proximal external region through interactions at the apex of HIV-1 Env.PLoS pathogens · 2022Article
- Global Increases in Human Immunodeficiency Virus Neutralization Sensitivity Due to Alterations in the Membrane-Proximal External Region of the Envelope Glycoprotein Can Be Minimized by Distant State 1-Stabilizing Changes.Journal of virology · 2022Article
- The endoplasmic reticulum proteostasis network profoundly shapes the protein sequence space accessible to HIV envelope.PLoS biology · 2022Article
- Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The human immunodeficiency virus type 1 (HIV-1) envelope trimer maintains a closed, metastable configuration to protect vulnerable epitopes from neutralizing antibodies. Here, we identify key hydrophobic constraints at the trimer apex that function as global stabilizers of the HIV-1 envelope spike configuration. Mutation of individual residues within four hydrophobic clusters that fasten together the V1V2, V3, and C4 domains at the apex of gp120 dramatically increases HIV-1 sensitivity to weak and restricted neutralizing antibodies targeting epitopes that are largely concealed in the prefusion Env spike, consistent with the adoption of a partially open trimer configuration. Conversely, the same mutations decrease the sensitivity to broad and potent neutralizing antibodies that preferentially recognize the closed trimer. Sera from chronically HIV-infected patients neutralize open mutants with enhanced potency, compared to the wild-type virus, suggesting that a large fraction of host-generated antibodies target concealed epitopes. The identification of structural constraints that maintain the HIV-1 envelope in an antibody-protected state may inform the design of a protective vaccine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.