Transcriptional and translational dynamics of Zika and Dengue virus infection Journal Article

Authors: Singh, K.; Martinez, M. G.; Lin, J.; Gregory, J.; Nguyen, T. U.; Abdelaal, R.; Kang, K.; Brennand, K.; Grünweller, A.; Ouyang, Z.; Phatnani, H.; Kielian, M.; Wendel, H. G.
Article Title: Transcriptional and translational dynamics of Zika and Dengue virus infection
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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: signal transduction; protein expression; nonhuman; gene expression; genetic transcription; virus rna; rna translation; cellular stress response; virus genome; oxidation reduction reaction; amino acid transfer rna ligase; open reading frame; growth arrest and dna damage inducible protein 153; dengue; protein kinase pim 1; endoplasmic reticulum stress; virus transcription; initiation factor 5a; polyamine metabolism; human; article; rna sequencing; atf3/chop; bach1/2; polyamine pathways; zikv
Journal Title: Viruses
Volume: 14
Issue: 7
ISSN: 1999-4915
Publisher: MDPI  
Date Published: 2022-07-01
Start Page: 1418
Language: English
DOI: 10.3390/v14071418
PROVIDER: scopus
PMCID: PMC9316442
PUBMED: 35891396
Notes: Article -- Export Date: 1 August 2022 -- Source: Scopus
Citation Impact
MSK Authors
  1. Hans Guido Wendel
    84 Wendel