CD154-CD40-induced reactivation of latent HIV-1 infection.
Kutsch, Olaf;
Levy, David N;
Kosloff, Barry R;
Shaw, George M;
Benveniste, Etty N;
(2003)
CD154-CD40-induced reactivation of latent HIV-1 infection.
Virology, 314 (1).
pp. 261-270.
ISSN 0042-6822
DOI: https://doi.org/10.1016/s0042-6822(03)00413-6
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Reservoirs of latent HIV-1 in T cells and macrophages pose one of the major obstacles that hamper final eradication of HIV-1 from infected patients. Targeting costimulatory molecules expressed on cell types harboring latent HIV-1 to achieve reactivation may provide a new approach to overcome this problem. One such molecule is CD40, a member of the tumor necrosis factor (TNF)-receptor family. Using THP89GFP cells as a model for latently infected macrophages, we demonstrate that trimeric forms of recombinant CD154 allow for the direct reactivation of latent HIV-1 infection. Reactivation is augmented by the release of TNF-alpha. The presence of TNF-alpha is also crucial for the expression of late structural genes such as p24 Gag. In addition, levels of secreted TNF-alpha are sufficiently high to reactivate latent HIV-1 in a latently HIV-1-infected T-cell line (J89GFP). Taken together, our results demonstrate that costimulatory molecules may be attractive targets to reactivate latent HIV-1 in infected patients.