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.
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.
Authors: Christian Schmitz; David Marchant; Stuart J D Neil; Keith Aubin; Sandra Reuter; Matthias T Dittmar; Aine McKnight Journal: J Virol Date: 2004-02 Impact factor: 5.103