title: Targeting NF-κB signaling with protein kinase C agonists as an emerging strategy for combating HIV latency.
abstract: Highly active antiretroviral therapy (HAART) is very effective in suppressing HIV-1 replication and restoring immune functions in HIV-infected individuals. However, it fails to eradicate the latent viral reservoirs and fully resolve chronic inflammation in HIV infection. The "shock-and-kill" strategy was recently proposed to induce latent HIV expression in the presence of HAART. Recent studies have shown that the protein kinase C (PKC) agonists are highly potent in inducing latent HIV expression from the viral reservoirs in vitro and ex vivo and in protecting primary CD4(+) T cells from HIV infection through down-modulation of their HIV coreceptor expression. The PKC agonists are excellent candidates for advancing to clinical HIV eradication strategies. This article will present a critical review of the structure and function of known PKC agonists, their mechanisms for the reactivation of latent HIV expression, and the potential of these compounds for advancing clinical HIV eradication strategies.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California , Davis, California.
authors.forename: Guochun
authors.initials: G
authors.lastname: Jiang
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004789:Enzyme Activation / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D015728:Receptors, HIV / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism; D017735:Virus Latency / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D010703:Phorbol Esters; D020569:Proto-Oncogene Proteins c-rel; D015728:Receptors, HIV; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D011493:Protein Kinase C