Elimination of HIV-1-Infected Primary T Cell Reservoirs in an In Vitro Model of Latency. Journal Article

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Authors: Rawlings, SA; Alonzo, F; Kozhaya, L; Torres, VJ; Unutmaz, D
Article Title: Elimination of HIV-1-Infected Primary T Cell Reservoirs in an In Vitro Model of Latency.
Abstract: Establishment of long-lived cellular reservoirs of HIV-1 represents a major therapeutic challenge to virus eradication. In this study, we utilized a human primary cell model of HIV-1 latency to evaluate the requirements for efficient virus reactivation from, and the selective elimination of, latently infected human T cells. Ectopic expression of BCL2 supported the replication and spread of R5-tropic HIV-1 in activated CD4(+) T cells. After IL-2 withdrawal, the HIV-1-infected T cells survived as resting cells for several months. Unexpectedly, these resting T cells continue to produce detectable levels of infectious virus, albeit at a lower frequency than cells maintained in IL-2. In the presence of HIV-1 inhibitors, reactivation of the resting T cells with ?c-cytokines and allogeneic dendritic cells completely extinguished HIV-1 infectivity. We also evaluated the ability of the bacterial LukED cytotoxin to target and kill CCR5-expressing cells. After ?c-cytokine stimulation, LukED treatment eliminated both HIV-1-infected resting cells and the non-infected CCR5+ cells. Importantly, complete clearance of in vitro HIV-1 reservoirs by LukED required a lower threshold of cytokine signals relative to HIV-1 inhibitors. Thus, the primary T cell-based HIV-1 latency model could facilitate the development of novel agents and therapeutic strategies that could effectively eradicate HIV-1.
Journal Title: PloS one
ISSN: 1932-6203; 1932-6203
Publisher: Unknown  
Date Published: 2015