Lars Pache, Miriam S Dutra, Adam M Spivak, John M Marlett, Jeffrey P Murry, Young Hwang, Ana M Maestre, Lara Manganaro, Mitchell Vamos, Peter Teriete, Laura J Martins, Renate König, Viviana Simon, Alberto Bosque, Ana Fernandez-Sesma, Nicholas D P Cosford, Frederic D Bushman, John A T Young, Vicente Planelles, Sumit K Chanda
Combination antiretroviral therapy (ART) is able to suppress HIV-1 replication to undetectable levels. However, the persistence of latent viral reservoirs allows for a rebound of viral load upon cessation of therapy. Thus, therapeutic strategies to eradicate the viral latent reservoir are critically needed. Employing a targeted RNAi screen, we identified the ubiquitin ligase BIRC2 (cIAP1), a repressor of the noncanonical NF-κB pathway, as a potent negative regulator of LTR-dependent HIV-1 transcription. Depletion of BIRC2 through treatment with small molecule antagonists known as Smac mimetics enhanced HIV-1 transcription, leading to a reversal of latency in a JLat latency model system...
September 9, 2015: Cell Host & Microbe