CD154-CD40-induced reactivation of latent HIV-1 infection.
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.
D019013:CD40 Antigens / Q000494:pharmacology*; D023201:CD40 Ligand / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D014775:Virus Activation; D017735:Virus Latency
D019013:CD40 Antigens; D023201:CD40 Ligand