Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected cells. Well-known immunoregulators including CSF2, IL-32, IL-6 and SERPINA3 were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1, PABPC1 and eIF4b, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

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: 
Tuesday, August 4, 2020
Research Area: