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Updated: Jul 10, 2026
Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
Relative concordance of human immunodeficiency virus oligomeric and monomeric envelope in CCR5 coreceptor usage
Samaporn Teeravechyan1, Pirada Suphaphiphat, Max Essex
1Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, MA 02115, USA.
Insights
Binding and fusion assays for human immunodeficiency virus (HIV) envelope proteins can yield different results. This study found that by controlling coreceptor binding kinetics, both assays provide comparable data on HIV envelope-CCR5 interactions.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Binding and fusion assays are crucial for studying human immunodeficiency virus (HIV) envelope protein interactions.
- Discrepancies in assay readouts for certain HIV envelope mutants suggest potential differences in how monomeric and oligomeric forms interact with coreceptors.
Purpose of the Study:
- To investigate whether observed discrepancies between HIV envelope binding and fusion assays stem from assay differences or genuine functional variations.
- To determine if monomeric envelope binding accurately reflects oligomeric envelope-CCR5 interactions.
Main Methods:
- Systematic study of HIV envelope regions involved in CCR5 coreceptor usage.
- Comparison of binding and fusion assay readouts for various HIV envelope mutants.
- Inclusion of the binding inhibitor TAK-779 in fusion assays to modulate coreceptor binding kinetics.
Main Results:
- Assay readouts became comparable when CCR5 binding kinetics were controlled using TAK-779.
- The study demonstrated that monomeric envelope binding correlates with oligomeric envelope-CCR5 interactions.
- Observed discordance between binding and fusion assays does not necessarily imply different coreceptor usage patterns.
Conclusions:
- Monomeric binding assays can effectively reflect oligomeric envelope-CCR5 interactions.
- Differences in assay readouts may be reconciled by accounting for binding kinetics, not necessarily distinct functional mechanisms.
- This finding clarifies the interpretation of data from binding versus fusion assays in HIV entry studies.
Abstract:
A major difference between binding and fusion assays commonly used to study the human immunodeficiency virus (HIV) envelope is the use of monomeric envelope for the former assay and oligomeric envelope for the latter. Due to discrepancies in their readouts for some mutants, envelope regions involved in CCR5 coreceptor usage were systematically studied to determine whether the discordance is due to inherent differences between the two assays or whether it genuinely reflects functional differences at each entry step. By adding the binding inhibitor TAK-779 to delay coreceptor binding kinetics in the fusion assay, the readouts were found comparable between the assays for the mutants analysed in this study. Our finding indicates that monomeric binding reflects oligomeric envelope-CCR5 interaction, thus discordant results between binding and fusion assays do not necessarily indicate differences in coreceptor usage by oligomeric envelope and monomeric gp120.
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