Single-cell transcriptional landscapes reveal HIV-1–driven aberrant host gene transcription as a potential therapeutic target
Runxia Liu, Yang-Hui Jimmy Yeh, Ales Varabyou, Jack A. Collora, Scott Sherrill-Mix, C. Conover Talbot, Sameet Mehta, Kristen Albrecht, Haiping Hao, Hao Zhang, Ross A. Pollack, Subul Beg, Rachela Calvi, Jianfei Hu, Christine M. Durand, Richard F. Ambinder, Rebecca Hoh, Steven G. Deeks, Jennifer Chiarella, Serena Spudich, Daniel C. Douek, Frederic D. Bushman, Mihaela Pertea, Ya‐Chi Ho
Abstract
). HIV-1-host RNA landscape analysis at the integration site revealed that HIV-1 drives high aberrant host gene transcription downstream, but not upstream, of the integration site through HIV-1-to-host aberrant splicing, in which HIV-1 RNA splices into the host RNA and aberrantly drives host RNA transcription. HIV-1-induced aberrant transcription was driven by the HIV-1 promoter as shown by CRISPR-dCas9-mediated HIV-1-specific activation and could be suppressed by CRISPR-dCas9-mediated inhibition of HIV-1 5' long terminal repeat. Overall, we identified cellular factors supporting HIV-1 reactivation and HIV-1-driven aberrant host gene transcription as potential therapeutic targets to disrupt HIV-1 persistence.