Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection

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 reponses, with ZIKV triggering a BACH1/2 redox program, and DENV activating the ETF/CHOP endoplasmatic 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 viral translation and replication. Concerning the viral RNA genomes, ribosome occupancy readily identifies 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 also the activation of RNA translation and polyamine metabolism during DENV and ZIKV infection. Overall design: We performed ribosome footprinting and RNA sequencing on human neuronal progenitor cells (hNPCs) cells either uninfected or infected with ZIKV or DENV in two biological replicates that were collected 72 hours post infection. Unifected samples are indicated as A1 and B1, ZIKV infected samples are indicated as A2, B2 and DENV infected samples are indicated as A3 and B3.