Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4+ T Cells

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. [Display omitted] •HIV-1-infected CD4+ T cells activate cellular survival programs•CD4+ T cells upregulate BIRC5 and OX40 during latent and productive HIV-1 infection•OX40+CD4+ T cells from ART-treated patients are enriched for clonal HIV-1 sequences•Inhibition of BIRC5 reduces the frequency of CD4+ T cells encoding for intact HIV-1 The host factors that promote the survival and persistence of HIV-infected CD4+ T cells are not clear. Kuo et al. demonstrate that the anti-apoptotic protein BIRC5 and its upstream regulator OX40 can promote survival of HIV-1-infected reservoir CD4+ T cells, specifically during clonal proliferation. These findings point to clinical strategies that may reduce persisting viral reservoirs.