A comprehensive map of the human dendritic cell HIV-response transcriptional network

• Published in: The Journal of immunology (1950) 2019-05, Vol.202 (1_Supplement), p.75-75.11
• Main Authors: Johnson, Jarrod S, De Veaux, Nicholas, Rives, Alexander W, Lahaye, Xavier, Lucas, Sasha Y, Pérot, Brieuc, Luka, Marine, Amon, Lynn M, Watters, Aaron, Aderem, Alan, Manel, Nicolas, Littman, Dan R, Bonneau, Richard, Ménager, Mickaël M
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.202.Supp.75.11

Transcriptional programming of the innate immune response is pivotal for host protection. However, the transcriptional mechanisms that link pathogen sensing with innate activation remain poorly understood. During infection with HIV-1, human dendritic cells (DCs) can detect the virus through an innate sensing pathway leading to antiviral type I interferon and DC maturation. Here, we have developed an iterative experimental and computational approach to map the innate response circuitry during HIV-1 infection. By integrating genome-wide chromatin accessibility with expression kinetics, we have inferred a gene regulatory network that links 542 transcription factors (TFs) with 21,862 target genes. Through genetic perturbation and drug treatments we identify PRDM1 and RARA as essential regulators of the interferon response and DC maturation, respectively. Our work provides a resource for interrogation of regulators of HIV replication and innate immunity, highlighting the complexity and cooperativity in the regulatory circuit controlling the DC response to HIV-1 infection.