Transcriptomic and epigenetic investigation of Zika virus (ZIKV) infection in human monocyte-derived dendritic cells and other cell types

Dendritic cells are key targets for ZIKV infection. To identify host pathways manipulated by ZIKV in dendritic cells, we developed a system that enables characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring, uninfected primary human dendritic cells. We first applied RNA-seq of ZIKV infected and uninfected bystander human monocyte-derived dendritic cells (moDCs) exposed to an unmodified clinical strain of ZIKV to identify ZIKV-regulated transcripts. We then applied a new genomic method recently developed by our group to sequence capped short mRNAs (csRNA-seq) in these cells. In addition to defining mRNA start sites at base pair resolution, this method also identifies transcriptionally active enhancers. Analysis of ZIKV-activated enhancers and promoters defined by csRNA-seq in infected moDCs revealed substantial enrichment for motifs recognized by sterol regulatory element binding proteins (SREBPs). Using ChIP-seq assays, we confirmed that in moDCs, ZIKV increased recruitment of SREBPs to lipid gene promoters and increased nascent expression of these genes.