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The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2-infected model cell lines and primary airway cells grown at an air-liquid interface to gain a deeper understanding...

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Autores principales: Puray-Chavez, Maritza, Lee, Nakyung, Tenneti, Kasyap, Wang, Yiqing, Vuong, Hung R., Liu, Yating, Horani, Amjad, Huang, Tao, Gunsten, Sean P., Case, James B., Yang, Wei, Diamond, Michael S., Brody, Steven L., Dougherty, Joseph, Kutluay, Sebla B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239271/
https://www.ncbi.nlm.nih.gov/pubmed/35604092
http://dx.doi.org/10.1128/mbio.00815-22
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author Puray-Chavez, Maritza
Lee, Nakyung
Tenneti, Kasyap
Wang, Yiqing
Vuong, Hung R.
Liu, Yating
Horani, Amjad
Huang, Tao
Gunsten, Sean P.
Case, James B.
Yang, Wei
Diamond, Michael S.
Brody, Steven L.
Dougherty, Joseph
Kutluay, Sebla B.
author_facet Puray-Chavez, Maritza
Lee, Nakyung
Tenneti, Kasyap
Wang, Yiqing
Vuong, Hung R.
Liu, Yating
Horani, Amjad
Huang, Tao
Gunsten, Sean P.
Case, James B.
Yang, Wei
Diamond, Michael S.
Brody, Steven L.
Dougherty, Joseph
Kutluay, Sebla B.
author_sort Puray-Chavez, Maritza
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2-infected model cell lines and primary airway cells grown at an air-liquid interface to gain a deeper understanding of the translationally regulated events in response to virus replication. We found that SARS-CoV-2 mRNAs dominate the cellular mRNA pool but are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy despite notable accumulation of ribosomes within the slippery sequence on the frameshifting element. In a highly permissive cell line model, although SARS-CoV-2 infection induced the transcriptional upregulation of numerous chemokine, cytokine, and interferon-stimulated genes, many of these mRNAs were not translated efficiently. The impact of SARS-CoV-2 on host mRNA translation was more subtle in primary cells, with marked transcriptional and translational upregulation of inflammatory and innate immune responses and downregulation of processes involved in ciliated cell function. Together, these data reveal the key role of mRNA translation in SARS-CoV-2 replication and highlight unique mechanisms for therapeutic development.
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spelling pubmed-92392712022-06-29 The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes Puray-Chavez, Maritza Lee, Nakyung Tenneti, Kasyap Wang, Yiqing Vuong, Hung R. Liu, Yating Horani, Amjad Huang, Tao Gunsten, Sean P. Case, James B. Yang, Wei Diamond, Michael S. Brody, Steven L. Dougherty, Joseph Kutluay, Sebla B. mBio Research Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2-infected model cell lines and primary airway cells grown at an air-liquid interface to gain a deeper understanding of the translationally regulated events in response to virus replication. We found that SARS-CoV-2 mRNAs dominate the cellular mRNA pool but are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy despite notable accumulation of ribosomes within the slippery sequence on the frameshifting element. In a highly permissive cell line model, although SARS-CoV-2 infection induced the transcriptional upregulation of numerous chemokine, cytokine, and interferon-stimulated genes, many of these mRNAs were not translated efficiently. The impact of SARS-CoV-2 on host mRNA translation was more subtle in primary cells, with marked transcriptional and translational upregulation of inflammatory and innate immune responses and downregulation of processes involved in ciliated cell function. Together, these data reveal the key role of mRNA translation in SARS-CoV-2 replication and highlight unique mechanisms for therapeutic development. American Society for Microbiology 2022-05-23 /pmc/articles/PMC9239271/ /pubmed/35604092 http://dx.doi.org/10.1128/mbio.00815-22 Text en Copyright © 2022 Puray-Chavez et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Puray-Chavez, Maritza
Lee, Nakyung
Tenneti, Kasyap
Wang, Yiqing
Vuong, Hung R.
Liu, Yating
Horani, Amjad
Huang, Tao
Gunsten, Sean P.
Case, James B.
Yang, Wei
Diamond, Michael S.
Brody, Steven L.
Dougherty, Joseph
Kutluay, Sebla B.
The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
title The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
title_full The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
title_fullStr The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
title_full_unstemmed The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
title_short The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
title_sort translational landscape of sars-cov-2-infected cells reveals suppression of innate immune genes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239271/
https://www.ncbi.nlm.nih.gov/pubmed/35604092
http://dx.doi.org/10.1128/mbio.00815-22
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