Drug screen combining RNA landscape analysis reveals targetable pathways in HIV-1 reactivation

We invesitgated cellular pathways required for HIV-1 activation using HIV-1-suppressing agents. Despite effective antiretroviral therapy, HIV-1-nfected cells continue to produce viral antigens and induce chronic immune exhaustion. Using a novel dual reporter system and a high-throughput drug screen, we identified FDA-approved drugs which can suppress HIV-1 reactivation in both cell line models and CD4+ T cells from virally suppressed, HIV-1-infected individuals. We identified 11 cellular pathways required for HIV-1 reactivation as druggable targets. Using differential expression analysis, gene set enrichment analysis and exon-intron landscape analysis, we examined the impact of drug treatment on the cellular environment at a genome-wide level. Drugs treatment of HIV-1-infected T cell clones and CD4+ T cells from HIV-1-infected individual under long term suppressive ARTs for 24 hours. Transcriptome analysis was performed on bulk mRNA from treated samples