Puray-Chavez et al. 2020 (PRJNA667051)

General Details

Title Translational landscape of SARS-CoV-2 and infected cells
Organism
Number of Samples 78
Release Date 2020/10/02 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP286182
ENA SRP286182
GEO GSE158930
BioProject PRJNA667051

Publication

Title
Authors Puray-Chavez M,Lee N,Tenneti K,Wang Y,Vuong HR,Liu Y,Horani A,Huang T,Gunsten SP,Case JB,Yang W,Diamond MS,Brody SL,Dougherty J,Kutluay SB
Journal mBio
Publication Date 2022 Jun 28
Abstract 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. IMPORTANCE SARS-CoV-2 utilizes a number of strategies to modulate host responses to ensure efficient propagation. Here, we used ribosome profiling in SARS-CoV-2-infected cells to gain a deeper understanding of the translationally regulated events in infected cells. We found that although viral mRNAs are abundantly expressed, they are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy and alternative translation initiation sites that help increase the coding potential of its RNAs. In permissive cells, SARS-CoV-2 infection induced the translational repression of numerous innate immune mediators. Though the impact of SARS-CoV-2 on host mRNA translation was more subtle in primary airway cell cultures, we noted marked transcriptional and translational upregulation of inflammatory and innate immune responses and downregulation of processes involved in ciliated cell function. Together, these data provide new insight into how SARS-CoV-2 modulates innate host responses and highlight unique mechanisms for therapeutic intervention.
PMC PMC9239271
PMID 35604092
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR12764729 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764730 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764731 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764732 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764733 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764734 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764735 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764736 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764737 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764738 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764739 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764740 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764753 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764754 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764755 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764756 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764757 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764758 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764759 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR12764760 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764761 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764762 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764763 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764764 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR12764777 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq chx_harr
SRR12764778 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764779 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764780 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764781 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764782 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764783 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq chx_harr
SRR12764784 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764785 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764786 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764787 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764788 PRJNA667051 Chlorocebus sabaeus Ribo-Seq chx_harr
SRR12764797 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764798 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764799 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764800 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764801 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764802 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764803 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764804 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764809 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764810 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764811 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR12764812 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324684 PRJNA667051 Chlorocebus sabaeus Vero Ribo-Seq Cycloheximide
SRR15324685 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR15324686 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR15324687 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR15324688 PRJNA667051 Chlorocebus sabaeus Ribo-Seq Cycloheximide
SRR15324714 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324715 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324716 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324717 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324718 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324719 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324720 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324721 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324722 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324723 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324724 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324725 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324726 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324727 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324728 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324729 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324730 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324731 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324732 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324733 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324734 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324735 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324736 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324737 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
SRR15324738 PRJNA667051 Homo sapiens Ribo-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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