Transcriptomic and epigenetic investigation of Zika virus (ZIKV) and Dengue virus (DENV) infection in human monocyte-derived dendritic cells

Dendritic cells are key targets for ZIKV and DENV infection. To identify host pathways manipulated by ZIKV and DENV in dendritic cells, we developed a system that enables characterization of genome-wide transcriptional and epigenetic changes in virus-infected and neighboring (bystander), uninfected primary human dendritic cells. We first applied RNA-seq of DENV or ZIKV infected and uninfected bystander human monocyte-derived dendritic cells (moDCs) exposed to unmodified clinical virus strains to identify virus-regulated transcripts. Using ChIP-seq assays, we confirmed that in moDCs, DENV increased recruitment of NF-kB to target gene promoters of DENV-induced genes. We then tested how ZIKV alters NF-kB induction of target genes in infected cells by treating with Kdo2-Lipid A (KLA).