Comparative transcriptomics highlights the role of the activator protein 1 transcription factor in the host response to Ebolavirus

James W. Wynne, Shawn Todd, Victoria Boyd, Mary Tachedjian, Reuben Klein, Brian Shiell, Megan Dearnley, Alexander J. McAuley, Amanda P. Woon, Anthony W. Purcell, Glenn A. Marsh, Michelle L. Baker

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Ebolavirus and Marburgvirus comprise two genera of negative-sense singlestranded RNA viruses that cause severe hemorrhagic fevers in humans. Despite considerable research efforts, the molecular events following Ebola virus (EBOV) infection are poorly understood. With the view of identifying host factors that underpin EBOV pathogenesis, we compared the transcriptomes of EBOV-infected human, pig, and bat kidney cells using a transcriptome sequencing (RNA-seq) approach. Despite a significant difference in viral transcription/replication between the cell lines, all cells responded to EBOV infection through a robust induction of extracellular growth factors. Furthermore, a significant upregulation of activator protein 1 (AP1) transcription factor complex members FOS and JUN was observed in permissive cell lines. Functional studies focusing on human cells showed that EBOV infection induces protein expression, phosphorylation, and nuclear accumulation of JUN and, to a lesser degree, FOS. Using a luciferase-based reporter, we show that EBOV infection induces AP1 transactivation activity within human cells at 48 and 72 h postinfection. Finally, we show that JUN knockdown decreases the expression of EBOV-induced host gene expression. Taken together, our study highlights the role of AP1 in promoting the host gene expression profile that defines EBOV pathogenesis.

Original languageEnglish
Article numbere01174-17
Number of pages21
JournalJournal of Virology
Volume91
Issue number23
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • AP1
  • Ebola virus
  • Ebolavirus
  • FOS
  • Growth factor
  • Host-pathogen interaction
  • JUN
  • RNA-seq

Cite this