The Journal of Immunology, Vol 156, Issue 10 3994-4004, Copyright © 1996 by American Association of Immunologists

ARTICLES

Binding of HIV-1 virions or gp120-anti-gp120 immune complexes to HIV-1- infected quiescent peripheral blood mononuclear cells reveals latent infection

L Briant, N Coudronniere, V Robert-Hebmann, M Benkirane and C Devaux
Laboratory of Retroviral Immunology, CNRS UPR9008, Montpellier, France.

HIV-1-infected quiescent CD4+ cells harbor the virus in an inactive state until subsequent activation. The possibility that HIV-1 itself and the virus envelope glycoprotein 120 (gp120) might be important agents of this activation was investigated. The present data indicate that binding of heat-inactivated HIV-1 (iHIV-1) to infected resting PBMCs was sufficient to activate NF-kappa B and AP-1, to induce transition from the G0/G1 stage of the cell cycle to the S/G2/M stage, to induce cell surface expression of CD25, to stimulate provirus integration, and to commit cells to produce virus. The cumulative amount of HIV-1 produced by iHIV-1-stimulated cells strictly depended on the concentration of p24gag in the virion preparations used for stimulation. Moreover, virus production was not evidenced in infected resting cells exposed to iHIV-1 previously incubated with soluble CD4 (sCD4), indicating that activation requires a contact between HIV-1 envelope glycoproteins and cell surface CD4. Although soluble gp120 did not stimulate virus production, we found that transition to the S/G2/M stage of the cell cycle, cell surface expression of activation Ags, and virus production were stimulated by cross-linking of CD4 by gp120-anti- gp120 immune complexes. Finally, incubation of gp120-anti-gp120 immune complexes with sCD4 inhibited these effects. These findings suggest that virions and gp120 anti-gp120 immune complexes found in infected patients at all times of infection can stimulate virus production in CD4+ cells harboring HIV-1 in an inducible state.

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