Ribosome-profiling reveals restricted post transcriptional expression 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 so understanding the host response is paramount. Transcriptomics has become incredibly important in unders...

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Bibliographic Details
Published inbioRxiv
Main Authors Alexander, Marina R, Brice, Aaron M, Petrus Jansen Van Vuren, Rootes, Christina L, Tribolet, Leon, Cowled, Christopher, Bean, Andrew G D, Stewart, Cameron R
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.03.2021
Subjects
Activating transcription factor 3
COVID-19
EGR-1 protein
Epithelial cells
Gene regulation
Host-pathogen interactions
Infections
Interleukin 6
mRNA stability
Pandemics
Post-transcription
Severe acute respiratory syndrome coronavirus 2
Transcription factors
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Summary: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 so understanding the host response 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 (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection. ### Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.03.03.433675