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Updated: Sep 27, 2026

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay
Published on: September 14, 2014
CD4-dependent and CD4-independent HIV-2: consequences for neutralization
Elaine R Thomas1, Christine Shotton, Robin A Weiss
1The Wohl Virion Centre, Windeyer Institute of Medical Sciences, University College London, London W1T 4JF, UK.
Background:
HIV-2 is less pathogenic than HIV-1. In contrast to HIV-1, many isolates of HIV-2, including primary isolates, can infect cells independently of CD4.
Objective:
To compare the sensitivity of CD4-dependent and CD4-independent isolates of HIV-2 to antibody-mediated neutralization.
Methods:
The neutralization sensitivity of CD4-dependent and CD4-independent molecular clones of HIV-2 to a panel of HIV-2-positive serum samples was tested. Monoclonal antibodies to various epitopes across the viral envelope were used to determine whether a specific epitope conferred neutralization sensitivity. Neutralization sensitivity of primary isolates of HIV-2 able to infect in the absence of cellular CD4 was also investigated. Antibody binding to sensitive and resistant envelopes was analysed using enzyme-linked immunosorbent assay and flow cytometry.
Results:
CD4-independent ROD B was highly sensitive to neutralization by HIV-2-positive sera compared with the CD4-dependent isolate ROD A. Induction of ROD A to infect CD4-negative cells by soluble CD4 rendered it equally sensitive to antibody neutralization. Similarly, primary X4, R5 or dual-tropic isolates of HIV-2 were significantly more susceptible to neutralization when utilizing a CD4-independent route of infection. Neutralization sensitivity was not epitope specific but several conformation-dependent antibodies accentuated this phenotype. Antibody binding to monomeric or oligomeric envelope did not correlate with neutralization sensitivity.
Conclusions:
HIV-2 isolates utilizing a CD4-independent route of infection are more sensitive to antibody-mediated neutralization. Cellular CD4 may protect HIV-2 from neutralization. This sensitivity to neutralization may, in part, explain the lower virus load and slower progression to disease in HIV-2-infected individuals.
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