PRJNA704763
Ribosome-profiling reveals restricted translation of antiviral cytokines and transcription factors during SARS-CoV-2 infection
The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus. Understanding host factors driving severity is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors and select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level. This early phase restriction of antiviral transcripts the lungs may contribute to higher viral loads and consequent immune dysregulation, typically seen in SARS-CoV-2 infection.