Genome-wide Bioinformatic Analyses Predict Key Host and Viral Factors in SARS-CoV-2 Pathogenesis

We analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes including CSF2, IL32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.

Authors: 
Mariana G. Ferrarini (University of Lyon, INSA-Lyon, INRA, BF2I, Villeurbanne, France)
Rita Rebollo (University of Lyon, INSA-Lyon, INRA, BF2I, Villeurbanne, France)
Andreas Gruber (Oxford Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK)
Andrea Guarracino (Centre for Molecular Bioinformatics, Department of Biology, University Of Rome Tor Vergata, Rome, Italy)
Itziar Martinez Gonzalez (Amsterdam UMC, Amsterdam, The Netherlands)
Taylor Floyd (Center for Neurogenetics, Weill Cornell Medicine, Cornell University, New York, NY, USA)
Daniel Siqueira de Oliveira (Laboratoire de Biométrie et Biologie Evolutive, Université de Lyon; Université Lyon 1; CNRS; UMR 5558, Villeurbanne, France)
Justin Shanklin (Brigham Young University, Provo, UT, USA)
Ethan Beausoleil (Brigham Young University, Provo, UT, USA)
Taneli Pusa (Laboratoire de Biométrie et Biologie Evolutive, Université de Lyon; Université Lyon 1; CNRS; UMR 5558, Villeurbanne, France)
Brett E. Pickett (Brigham Young University, Provo, UT, USA)
Vanessa Aguiar-Pulido (Center for Neurogenetics, Weill Cornell Medicine, Cornell University, New York, NY, USA)
Publication Date: 
Monday, May 17, 2021
Research Area: