@article{4dfa1c33330c410b9b7e069135cf5883,
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.",
keywords = "ATF3/CHOP, BACH1/2, ZIKV, dengue, polyamine pathways",
author = "Kamini Singh and Martinez, {Maria G.} and Jianan Lin and James Gregory and Nguyen, {Trang Uyen} and Rawan Abdelaal and Kristy Kang and Kristen Brennand and Arnold Gr{\"u}nweller and Zhengqing Ouyang and Hemali Phatnani and Margaret Kielian and Wendel, {Hans Guido}",
note = "Funding Information: HGW is supported by NIH/NCI grants R01CA183876-03, R01 CA207217-04, R01CA190384-05, P50 CA217694-02, P50 CA192937-04, P30 CA008748 CRAIG THOMPSON GRANT, R35 CA252982, P50 CA217694 SPORE, and P50 CA192937. HGW is supported by Lymphoma Research Foundation; William H. Goodwin and Mrs. Alice Goodwin and the Common-wealth Foundation for Cancer Research; the Center for Experimental Therapeutics at MSKCC; the Starr Cancer Consortium; the Geoffrey Beene Cancer Research Center; David Rubenstein Center for Pancreatic Cancer; Druckenmiller Center for Lung Cancer Research; a Leukemia and Lymphoma Society (LLS) SPORE grant; and the MSKCC Core Grant (P30 CA008748). H.G.W. is a scholar of the Leukemia Lymphoma Society. KS is supported by the Pancreatic Cancer Action Network. ZO is supported by NIH R35 GM124998. AG was supported by the LOEWE Center DRUID (project A2). This work was supported by grants to M.K. from the National Institute of General Medical Sciences (R01GM057454) and the National Institute of Allergy and Infectious Diseases (R01AI075647). Funding Information: Funding: HGW is supported by NIH/NCI grants R01CA183876-03, R01 CA207217-04, R01CA190384-05, P50 CA217694-02, P50 CA192937-04, P30 CA008748 CRAIG THOMPSON GRANT, R35 CA252982, P50 CA217694 SPORE, and P50 CA192937. HGW is supported by Lymphoma Research Foundation; William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research; the Center for Experimental Therapeutics at MSKCC; the Starr Cancer Consortium; the Geoffrey Beene Cancer Research Center; David Rubenstein Center for Pancreatic Cancer; Druckenmiller Center for Lung Cancer Research; a Leukemia and Lymphoma Society (LLS) SPORE grant; and the MSKCC Core Grant (P30 CA008748). H.G.W. is a scholar of the Leukemia Lymphoma Society. KS is supported by the Pancreatic Cancer Action Network. ZO is supported by NIH R35 GM124998. AG was supported by the LOEWE Center DRUID (project A2). This work was supported by grants to M.K. from the National Institute of General Medical Sciences (R01GM057454) and the National Institute of Allergy and Infectious Diseases (R01AI075647). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2022",
month = jul,
doi = "10.3390/v14071418",
language = "English (US)",
volume = "14",
journal = "Viruses",
issn = "1999-4915",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "7",
}