In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 12 ( 2021-12-21), p. e3001065-
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001065
DOI:
10.1371/journal.pbio.3001065.g001
DOI:
10.1371/journal.pbio.3001065.g002
DOI:
10.1371/journal.pbio.3001065.g003
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10.1371/journal.pbio.3001065.g004
DOI:
10.1371/journal.pbio.3001065.g005
DOI:
10.1371/journal.pbio.3001065.g006
DOI:
10.1371/journal.pbio.3001065.g007
DOI:
10.1371/journal.pbio.3001065.t001
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10.1371/journal.pbio.3001065.s001
DOI:
10.1371/journal.pbio.3001065.s002
DOI:
10.1371/journal.pbio.3001065.s003
DOI:
10.1371/journal.pbio.3001065.s004
DOI:
10.1371/journal.pbio.3001065.s005
DOI:
10.1371/journal.pbio.3001065.s006
DOI:
10.1371/journal.pbio.3001065.s007
DOI:
10.1371/journal.pbio.3001065.s008
DOI:
10.1371/journal.pbio.3001065.s009
DOI:
10.1371/journal.pbio.3001065.s010
DOI:
10.1371/journal.pbio.3001065.s011
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10.1371/journal.pbio.3001065.s012
DOI:
10.1371/journal.pbio.3001065.s013
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10.1371/journal.pbio.3001065.s014
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10.1371/journal.pbio.3001065.s015
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10.1371/journal.pbio.3001065.s016
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10.1371/journal.pbio.3001065.s017
DOI:
10.1371/journal.pbio.3001065.s018
DOI:
10.1371/journal.pbio.3001065.s019
DOI:
10.1371/journal.pbio.3001065.r001
DOI:
10.1371/journal.pbio.3001065.r002
DOI:
10.1371/journal.pbio.3001065.r003
DOI:
10.1371/journal.pbio.3001065.r004
DOI:
10.1371/journal.pbio.3001065.r005
DOI:
10.1371/journal.pbio.3001065.r006
DOI:
10.1371/journal.pbio.3001065.r007
DOI:
10.1371/journal.pbio.3001065.r008
DOI:
10.1371/journal.pbio.3001065.r009
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X