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.

Original languageEnglish
Issue number3
StatePublished - Jun 2022


  • SARS-CoV-2
  • immune response
  • mRNA translation
  • programmed frameshifting
  • ribo-seq
  • ribosomal frameshifting
  • ribosome profiling
  • translational repression
  • virus replication
  • virus-host interaction


Dive into the research topics of 'The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes'. Together they form a unique fingerprint.

Cite this