The translational landscape of SARS-CoV-2 and infected cells.

Autor: Puray-Chavez M; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Lee N; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Tenneti K; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Wang Y; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Vuong HR; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Liu Y; Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA., Horani A; Department of Pediatrics, Allergy, Immunology and Pulmonary Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Huang T; Department of Medicine, Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Gunsten SP; Department of Medicine, Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Case JB; Department of Medicine, Infectious Disease Division, Washington University School of Medicine, Saint Louis, MO 63110, USA., Yang W; Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA., Diamond MS; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Medicine, Infectious Disease Division, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Pathology & Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Brody SL; Department of Medicine, Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO 63110, USA., Dougherty J; Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, USA.; Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA., Kutluay SB; Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Oct 07. Date of Electronic Publication: 2021 Oct 07.
DOI: 10.1101/2020.11.03.367516
Abstrakt: 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 the air-liquid interface to gain a deeper understanding of the translationally regulated events in response to virus replication. We find 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 in comparison to HIV-1, suggesting utilization of distinct structural elements. In the highly permissive cell models, although SARS-CoV-2 infection induced the transcriptional upregulation of numerous chemokines, cytokines and interferon stimulated genes, many of these mRNAs were not translated efficiently. 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.
Databáze: MEDLINE
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