CD4-dependent and CD4-independent HIV-2: consequences for neutralization.
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.
Thomas
Elaine R
ER
The Wohl Virion Centre, Windeyer Institute of Medical Sciences, University College London, London W1T 4JF, UK.
Shotton
Christine
C
Weiss
Robin A
RA
Clapham
Paul R
PR
McKnight
Aine
A
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D019562:Viral Load
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120