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Updated: Sep 20, 2025

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay

Published on: September 14, 2014

Structural dynamics reveal isolate-specific differences at neutralization epitopes on HIV Env.

Edgar A Hodge¹, Gajendra S Naika¹, Sally M Kephart¹

¹Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.

|June 9, 2022

Summary

This summary is machine-generated.

HIV envelope glycoprotein (Env) dynamics vary significantly between isolates, impacting antibody neutralization. Hydrogen/deuterium-exchange mass spectrometry revealed isolate-specific conformational changes and epitope accessibility differences in Env trimers.

Keywords:

Immunology Microbiology Structural biology

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Area of Science:

Virology
Structural Biology
Immunology

Background:

The HIV envelope glycoprotein (Env) is crucial for viral entry and a primary target for neutralizing antibodies.
While static structures show similarity, Env's dynamic nature is key to its variability and immune evasion.
Understanding Env dynamics is vital for developing effective HIV therapies and vaccines.

Purpose of the Study:

To map local dynamics of native-like HIV Env SOSIP trimers from diverse isolates.
To investigate how dynamic differences influence antibody binding and neutralization sensitivity.
To assess the impact of stabilizing mutations on Env dynamics across different isolates.

Main Methods:

Utilized hydrogen/deuterium-exchange mass spectrometry (HDX-MS) to analyze Env trimer dynamics.
Studied native-like Env SOSIP trimers derived from various HIV isolates.
Investigated the effect of hyper-stabilizing mutations on Env dynamics.

Main Results:

Significant variations in epitope accessibility were observed across different HIV isolates.
Isolate-dependent conformational switching of Env was detected across a wide range of timescales.
Hyper-stabilizing mutations showed variable effects on Env dynamics, depending on the isolate.

Conclusions:

HIV Env dynamics are highly isolate-specific and influence antibody target sites.
Conformational flexibility plays a critical role in HIV's immune evasion strategies.
Targeting Env dynamics may offer new avenues for HIV vaccine and therapeutic development.