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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/7/1418 |
| _version_ | 1797443167805505536 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kamini Singh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T12:52:08Z |
| format | Article |
| id | doaj.art-97db0caa53a3485ba9d516d0d9e2a0ff |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T12:52:08Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-97db0caa53a3485ba9d516d0d9e2a0ff2023-11-30T22:04:47ZengMDPI AGViruses1999-49152022-06-01147141810.3390/v14071418Transcriptional and Translational Dynamics of Zika and Dengue Virus InfectionKamini Singh0Maria Guadalupe Martinez1Jianan Lin2James Gregory3Trang Uyen Nguyen4Rawan Abdelaal5Kristy Kang6Kristen Brennand7Arnold Grünweller8Zhengqing Ouyang9Hemali Phatnani10Margaret Kielian11Hans-Guido Wendel12Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USADepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USAThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032 and Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USADepartment of Neurology, Vagelos College of Physicians & Surgeons of Columbia University, New York, NY 10032, USADepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Albert Einstein Cancer, Center, Bronx, NY 10461, USADepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Neurology, Vagelos College of Physicians & Surgeons of Columbia University, New York, NY 10032, USADivision of Molecular Psychiatry, Departments of Psychiatry and Genetics, Yale School of Medicine, New Haven, CT 06510, USAInstitute of Pharmaceutical Chemistry, Philipps University Marburg, 35032 Marburg, GermanyDepartment of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USADepartment of Neurology, Vagelos College of Physicians & Surgeons of Columbia University, New York, NY 10032, USADepartment of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USACancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USAZika 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.https://www.mdpi.com/1999-4915/14/7/1418ZIKVpolyamine pathwaysATF3/CHOPBACH1/2dengueeIF5A hypusination |
| spellingShingle | 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 Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection Viruses ZIKV polyamine pathways ATF3/CHOP BACH1/2 dengue eIF5A hypusination |
| title | Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection |
| title_full | Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection |
| title_fullStr | Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection |
| title_full_unstemmed | Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection |
| title_short | Transcriptional and Translational Dynamics of Zika and Dengue Virus Infection |
| title_sort | transcriptional and translational dynamics of zika and dengue virus infection |
| topic | ZIKV polyamine pathways ATF3/CHOP BACH1/2 dengue eIF5A hypusination |
| url | https://www.mdpi.com/1999-4915/14/7/1418 |
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