Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection

Echavarría-Consuegra, Liliana; Cook, Georgia M; Busnadiego, Idoia; Lefèvre, Charlotte; Keep, Sarah; Brown, Katherine; Doyle, Nicole; Dowgier, Giulia; Franaszek, Krzysztof; Moore, Nathan A; Siddell, Stuart G; Bickerton, Erica; Hale, Benjamin G; Firth, Andrew E; Brierley, Ian; Irigoyen, Nerea

doi:10.1371/journal.ppat.1009644

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Echavarría-Consuegra, L., Cook, G. M., Busnadiego, I., Lefèvre, C., Keep, S., Brown, K., Doyle, N., Dowgier, G., Franaszek, K., Moore, N. A., Siddell, S. G., Bickerton, E., Hale, B. G., Firth, A. E., Brierley, I., & Irigoyen, N. (2021). Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection. PLoS Pathogens, 17(6), e1009644. https://doi.org/10.1371/journal.ppat.1009644

Abstract

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most s