Abstract
HIV-1 infection of CD4+ Tcells 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+ Tcells and were functionally involved in maintaining their viability. Moreover, OX40-expressing CD4+ Tcells from ART-treated patients were enriched for clonally expanded HIV-1sequences, and pharmacological inhibition of BIRC5 resulted in a selective decrease of HIV-1-infected cells invitro. 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.
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