Document Type

Article

Publication Date

6-28-2022

Publication Title

Viruses

Keywords

JGM, Dengue, Dengue Virus, Humans, Polyamines, RNA, Viral, Zika Virus, Zika Virus Infection

JAX Source

Viruses. 2022;14(7):1418

Volume

14

Issue

7

First Page

1418

ISSN

1999-4915

PMID

35891396

DOI

https://doi.org/10.3390/v14071418

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 footprinting 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 infection.

Comments

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

Download

Share

COinS