|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Kuo, H-H, Ahmad, R, Lee, GQ, Gao, C, Chen, H-R, Ouyang, Z, Szucs, MJ, Kim, D, Tsibris, A, Chun, T-W, Battivelli, E, Verdin, E, Rosenberg, ES, Carr, SA, Yu, XG, Lichterfeld, M|
|Date Published||2018 May 15|
HIV-1 infection of CD4 T cells leads to cytopathic effects and cell demise, which is counter to the observation that certain HIV-1-infected cells possess a remarkable long-term stability and can persist lifelong in infected individuals treated with suppressive antiretroviral therapy (ART). Using quantitative mass spectrometry-based proteomics, we showed that HIV-1 infection activated cellular survival programs that were governed by BIRC5, a molecular inhibitor of cell apoptosis that is frequently overexpressed in malignant cells. BIRC5 and its upstream regulator OX40 were upregulated in productively and latently infected CD4 T cells and were functionally involved in maintaining their viability. Moreover, OX40-expressing CD4 T cells from ART-treated patients were enriched for clonally expanded HIV-1 sequences, and pharmacological inhibition of BIRC5 resulted in a selective decrease of HIV-1-infected cells in vitro. Together, these findings suggest that BIRC5 supports long-term survival of HIV-1-infected cells and may lead to clinical strategies to reduce persisting viral reservoirs.
|Grant List||R01 AI098487 / AI / NIAID NIH HHS / United States |
R01 AI120008 / AI / NIAID NIH HHS / United States
R01 AI130005 / AI / NIAID NIH HHS / United States