TY - JOUR
AU - Herder, Vanessa
AU - Dee, Kieran
AU - Wojtus, Joanna K.
AU - Epifano, Ilaria
AU - Goldfarb, Daniel M.
AU - Rozario, Christoforos
AU - Gu, Quan
AU - da Silva Filipe, Ana
AU - Nomikou, Kyriaki
AU - Nichols, Jenna
AU - Jarrett, Ruth F.
AU - Stevenson, Andrew
AU - McFarlane, Steven
AU - Stewart, Meredith
AU - Szemiel, Agnieszka M.
AU - Pinto, Rute Maria
AU - Masdefiol Garriga, Andreu
AU - Davis, Chris
AU - Allan, Jay
AU - Graham, Sheila V.
AU - Murcia, Pablo R.
AU - Boutell, Chris
PY - 2021
DA - December
TI - Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defences
JO - PLoS Biology
VL - 19
IS - 12
DO - http://dx.doi.org/10.1371/journal.pbio.3001065
AB - 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.
PB - Public Library of Science
UR - http://eprints.gla.ac.uk/261021/
KW - Coronavirus (COVID-19)
ER