Genome-wide RNA-seq and Epigenetic analysis of human monocyte derived macrophage responses to Zika virus infection

Interpretation of genome-wide investigations of host-pathogen interactions are often obscured by analyses of mixed populations of infected and uninfected cells. Thus, we developed a system whereby we simultaneously characterize and compare genome-wide transcriptional and epigenetic changes in pure populations of virally-infected and neighboring uninfected cells to identify viral-regulated host-responses. Using patient-derived unmodified Zika viruses (ZIKV) infecting primary human macrophages, we reveal that ZIKV suppresses host transcription by multiple mechanisms. ZIKV infection causes both targeted suppression of type I interferon responses and general suppression by reducing RNA polymerase II protein levels and DNA occupancy. Simultaneous evaluation of transcriptomic and epigenetic features of infected and uninfected cells provide a powerful method for identifying coincident evolution of dominant pro-viral or anti-viral mechanisms. Analysis of transcriptional and epigenetic response of human monocyte derived macrophages to Zika virus infection