Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection

Kamini Singh, Maria Guadalupe Martinez, Jianan Lin, James Gregory, Trang Uyen Nguyen, Rawan Abdelaal, Kristy Kang, Kristen Brennand, Arnold Grünweller, Zhengqing Ouyang, Hemali Phatnani, Margaret Kielian, Hans Guido Wendel

Research output: Contribution to journalArticlepeer-review

Abstract

Zika virus (ZIKV) and dengue virus (DENV) are members of the Flaviviridae family of RNA viruses and cause severe disease in humans. ZIKV and DENV share over 90% of their genome sequences, however, the clinical features of Zika and dengue infections are very different reflecting tropism and cellular effects. Here, we used simultaneous RNA sequencing and ribosome footprint-ing to define the transcriptional and translational dynamics of ZIKV and DENV infection in human neuronal progenitor cells (hNPCs). The gene expression data showed induction of aminoacyl tRNA synthetases (ARS) and the translation activating PIM1 kinase, indicating an increase in RNA translation capacity. The data also reveal activation of different cell stress responses, with ZIKV triggering a BACH1/2 redox program, and DENV activating the ATF/CHOP endoplasmic reticulum (ER) stress program. The RNA translation data highlight activation of polyamine metabolism through changes in key enzymes and their regulators. This pathway is needed for eIF5A hypusination and has been implicated in viral translation and replication. Concerning the viral RNA genomes, ribosome occupancy readily identified highly translated open reading frames and a novel upstream ORF (uORF) in the DENV genome. Together, our data highlight both the cellular stress response and the activation of RNA translation and polyamine metabolism during DENV and ZIKV infec-tion.

Original languageEnglish (US)
Article number1418
JournalViruses
Volume14
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • ATF3/CHOP
  • BACH1/2
  • ZIKV
  • dengue
  • polyamine pathways

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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