The Translational Landscape of SARS-CoV-2-infected Cells Reveals Suppression of Innate Immune Genes
Maritza Puray‐Chavez, Nakyung Lee, Kasyap Tenneti, Yiqing Wang, Hung R. Vuong, Yating Liu, Amjad Horani, Tao Huang, Sean P. Gunsten, James Brett Case, Wei Yang, Michael Diamond, Steven L. Brody, Joseph D. Dougherty, Sebla B. Kutluay
Abstract
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.