Binding of HIV-1 virions or gp120-anti-gp120 immune complexes to HIV-1-infected quiescent peripheral blood mononuclear cells reveals latent infection.
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.
Briant
L
L
Laboratory of Retroviral Immunology, CNRS UPR9008, Montpellier, France.
Coudronnière
N
N
Robert-Hebmann
V
V
Benkirane
M
M
Devaux
C
C
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016679:Genome, Viral; D015483:HIV Antibodies / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007399:Interphase / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014771:Virion / Q000276:immunology / Q000378:metabolism*; D016662:Virus Integration / Q000276:immunology; D017735:Virus Latency / Q000276:immunology*
D000936:Antigen-Antibody Complex; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D016328:NF-kappa B; D018808:Transcription Factor AP-1