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

• Published in: The Journal of immunology (1950) Vol. 156; no. 10; pp. 3994 - 4004
• Main Authors: Briant, L, Coudronniere, N, Robert-Hebmann, V, Benkirane, M, Devaux, C
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.1996
• Subjects: AIDS/HIV; Antigen-Antibody Complex - metabolism; Base Sequence; CD8-Positive T-Lymphocytes - immunology; Genome, Viral; HIV Antibodies - metabolism; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - metabolism; human immunodeficiency virus 1; Humans; Interphase - immunology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation; Lymphocyte Depletion; Molecular Sequence Data; NF-kappa B - metabolism; Transcription Factor AP-1 - metabolism; Transcription, Genetic - immunology; Virion - immunology; Virion - metabolism; Virus Integration - immunology; Virus Latency - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.156.10.3994

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.