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Updated: Jul 29, 2025
07:10
Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
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Temsavir Modulates HIV-1 Envelope Conformation by Decreasing Its Proteolytic Cleavage
Marianne Boutin1,2, Halima Medjahed1, Manon Nayrac1,2
1Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada.
Viruses
|May 27, 2023
Summary
Temsavir, an HIV-1 inhibitor, stabilizes the virus's envelope glycoprotein (Env) in a closed state. This stabilization impacts Env processing, affecting antibody recognition and the potential for antibody-dependent cellular cytotoxicity (ADCC).
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- HIV-1 envelope glycoproteins (Envs) are crucial for viral entry and are key targets for therapeutic interventions.
- Temsavir (BMS-626529) is a small molecule inhibitor that targets Env by binding to the gp120 subunit, preventing CD4 interaction and stabilizing Env in a closed conformation.
- Previous studies indicated temsavir influences Env glycosylation, proteolytic processing, and conformation.
Purpose of the Study:
- To investigate the impact of temsavir on the conformation and processing of a diverse panel of primary HIV-1 Envs and infectious molecular clones (IMCs).
- To determine the relationship between temsavir's effect on Env processing and the recognition of HIV-1-infected cells by broadly neutralizing antibodies.
- To assess the correlation between temsavir-induced changes in Env processing and the mediation of antibody-dependent cellular cytotoxicity (ADCC).
Main Methods:
- Treatment of HIV-1 primary Envs and IMCs with temsavir.
- Analysis of Env cleavage and conformational changes using various biochemical and immunological assays.
- Evaluation of the recognition of temsavir-treated HIV-1-infected cells by a panel of broadly neutralizing antibodies.
- Assessment of antibody-dependent cellular cytotoxicity (ADCC) mediated by antibodies against temsavir-treated cells.
Main Results:
- Temsavir demonstrated a heterogeneous impact on Env cleavage and conformation across different primary Envs and IMCs.
- The observed effects of temsavir on Env conformation were associated with a decrease in Env processing (cleavage).
- Temsavir-induced alterations in Env processing influenced the binding of broadly neutralizing antibodies to HIV-1-infected cells.
- Changes in Env processing correlated with the capacity of antibodies to mediate ADCC.
Conclusions:
- Temsavir's mechanism of action extends beyond blocking viral entry to include modulation of Env processing and conformation.
- The impact of temsavir on Env processing affects antibody recognition and effector functions like ADCC, suggesting implications for therapeutic strategies.
- Understanding temsavir's influence on Env processing is critical for predicting treatment efficacy and developing next-generation HIV-1 inhibitors.
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