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
Affiliations
Kamini Singh
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
Maria Guadalupe Martinez
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Jianan Lin
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032 and Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA
James Gregory
Department of Neurology, Vagelos College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA
Trang Uyen Nguyen
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Albert Einstein Cancer, Center, Bronx, NY 10461, USA
Rawan Abdelaal
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Kristy Kang
Department of Neurology, Vagelos College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA
Kristen Brennand
Division of Molecular Psychiatry, Departments of Psychiatry and Genetics, Yale School of Medicine, New Haven, CT 06510, USA
Arnold Grünweller
Institute of Pharmaceutical Chemistry, Philipps University Marburg, 35032 Marburg, Germany
Zhengqing Ouyang
Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA
Hemali Phatnani
Department of Neurology, Vagelos College of Physicians & Surgeons of Columbia University, New York, NY 10032, USA
Margaret Kielian
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Hans-Guido Wendel
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
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.
