Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defences

Herder, V. et al. (2021) Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defences. PLoS Biology, 19(12), e3001065. (doi: 10.1371/journal.pbio.3001065) (PMID:34932557) (PMCID:PMC8765667)

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Abstract

The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41°C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air–liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40°C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.

Item Type:Articles
Additional Information:Funding: VH was funded by the German Research Foundation (Deutsche Forschungsgemeinschaft; project number 406109949) and the Federal Ministry of Food and Agriculture (BMEL; Förderkennzeichen: 01KI1723G). KD and PRM were funded by the Medical Research Council (MRC; MC_UU_12014/9 to PRM). JKW was funded by an MRC CVR DTA award (MC_ST_U18018). IE was funded by a CSO project grant (TCS/19/11). DG was funded by an MRC-DTP award (MR/R502327/1). CR was funded by a BBSRC-CTP award (BB/R505341/1). QG was funded by the MRC (MC_UU_12014/12). KN and ASF were funded by the MRC (MC_UU_12018/12). MES was funded by the MRC (MC PC 19026). AMS was funded by a UKRI/DHSC grant (BB/R019843/1 to Brian Willett, MRC-UoG CVR) and MRC CoV supplement grant (MC_PC_19026). RMP was funded by the MRC (MC_UU_12014/10). AMG was funded by studentship awards from the University of Glasgow School of Veterinary Medicine (Georgina D. Gardner, 145813; John Crawford, 123939). CB and SMF were funded by the MRC (MC_UU_12014/5 to CB).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jarrett, Professor Ruth and Davis, Dr Chris and Wojtus, Miss Joanna and Da Silva Filipe, Dr Ana and Masdefiol Garriga, Andreu and Goldfarb, Mr Daniel and Epifano, Dr Ilaria and Gu, Dr Quan and Allan, Mr Jay and Graham, Professor Sheila and Szemiel, Dr Agnieszka and Herder, Dr Vanessa and Stevenson, Mr Andrew and Rozario, Christoforos and Pinto, Dr Rute and McFarlane, Mr Steven and Nichols, Mrs Jenna and Nomikou, Dr Kyriaki and Boutell, Dr Chris and Stewart, Dr Meredith and Murcia, Professor Pablo and Dee, Dr Kieran
Authors: Herder, V., Dee, K., Wojtus, J. K., Epifano, I., Goldfarb, D., Rozario, C., Gu, Q., Da Silva Filipe, A., Nomikou, K., Nichols, J., Jarrett, R. F., Stevenson, A., McFarlane, S., Stewart, M., Szemiel, A., Pinto, R. M., Masdefiol Garriga, A., Davis, C., Allan, J., Graham, S. V., Murcia, P. R., and Boutell, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS Biology
Publisher:Public Library of Science
ISSN:1544-9173
ISSN (Online):1545-7885
Published Online:21 December 2021
Copyright Holders:Copyright © 2021 Herder et al.
First Published:First published in PLoS Biology 2021
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630Quinquennial Core FundsMassimo PalmariniMedical Research Council (MRC)MC_UU_12014/9III-MRC-GU CVR Support Services
Medical Research Council (MRC)MC_ST_U18018
Office of the Chief Scientific Adviser (CSO)TCS/19/11
313949National Productivity Investment Fund StudentshipsGeorge BaillieMedical Research Council (MRC)MR/R502327/1MVLS - Graduate School
Medical Research Council (MRC)MC_UU_12014/12
302172A One Health approach to pan-valent morbillivirus vaccinesBrian WillettBiotechnology and Biological Sciences Research Council (BBSRC)BB/R019843/1III - Centre for Virus Research
Medical Research Council (MRC)MC_PC_19026
Medical Research Council (MRC)MC_UU_12014/10
Medical Research Council (MRC)MC_UU_12014/5