Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages

Aaron F. Carlin, Edward A. Vizcarra, Emilie Branche, Karla M. Viramontes, Lester Suarez-Amaran, Klaus Ley, Sven Heinz, Christopher Benner, Sujan Shresta, Christopher K. Glass

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Genome-wide investigations of host-pathogen interactions are often limited by analyses of mixed populations of infected and uninfected cells, which lower sensitivity and accuracy. To overcome these obstacles and identify key mechanisms by which Zika virus (ZIKV) manipulates host responses, we developed a system that enables simultaneous characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring uninfected primary human macrophages. We demonstrate that transcriptional responses in ZIKV-infected macrophages differed radically from those in uninfected neighbors and that studying the cell population as a whole produces misleading results. Notably, the uninfected population of macrophages exhibits the most rapid and extensive changes in gene expression, related to type I IFN signaling. In contrast, infected macrophages exhibit a delayed and attenuated transcriptional response distinguished by preferential expression of IFNB1 at late time points. Biochemical and genomic studies of infected macrophages indicate that ZIKV infection causes both a targeted defect in the type I IFN response due to degradation of STAT2 and reduces RNA polymerase II protein levels and DNA occupancy, particularly at genes required for macrophage identity. Simultaneous evaluation of transcriptomic and epigenetic features of infected and uninfected macrophages thereby reveals the coincident evolution of dominant proviral or antiviral mechanisms, respectively, that determine the outcome of ZIKV exposure.

Original languageEnglish (US)
Pages (from-to)E9172-E9181
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
StatePublished - Sep 25 2018
Externally publishedYes


  • Genomics
  • Immune evasion
  • Macrophage
  • Transcription
  • Zika virus

ASJC Scopus subject areas

  • General


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