Abstract
Since its emergence in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally and become a major public health burden. Despite its close phylogenetic relationship to SARS-CoV, SARS-CoV-2 exhibits increased human-to-human transmission dynamics, likely due to efficient early replication in the upper respiratory epithelium of infected individuals. Since different temperatures encountered in the human upper and lower respiratory tract (33°C and 37°C, respectively) have been shown to affect the replication kinetics of several respiratory viruses, as well as host innate immune response dynamics, we investigated the impact of temperature on SARS-CoV-2 and SARS-CoV infection using the primary human airway epithelial cell culture model. SARS-CoV-2, in contrast to SARS-CoV, replicated to higher titers when infections were performed at 33°C rather than 37°C. Although both viruses were highly sensitive to type I and type III interferon pretreatment, a detailed time-resolved transcriptome analysis revealed temperature-dependent interferon and pro-inflammatory responses induced by SARS-CoV-2 that were inversely proportional to its replication efficiency at 33°C or 37°C. These data provide crucial insight on pivotal virus-host interaction dynamics and are in line with characteristic clinical features of SARS-CoV-2 and SARS-CoV, as well as their respective transmission efficiencies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / pharmacology
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Cells, Cultured
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Chlorocebus aethiops
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Epithelial Cells / virology
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Gene Expression Profiling / methods*
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Gene Expression Regulation, Viral / drug effects
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Gene Expression Regulation, Viral / genetics*
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Host-Pathogen Interactions / drug effects
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Host-Pathogen Interactions / genetics
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Humans
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Interferons / pharmacology
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SARS-CoV-2 / drug effects
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SARS-CoV-2 / genetics*
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SARS-CoV-2 / physiology
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Severe acute respiratory syndrome-related coronavirus / drug effects
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Severe acute respiratory syndrome-related coronavirus / genetics*
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Severe acute respiratory syndrome-related coronavirus / physiology
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Species Specificity
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Temperature
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Vero Cells
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Virus Replication / drug effects
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Virus Replication / genetics
Substances
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Antiviral Agents
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Interferons
Grants and funding
The authors received funding from the following sources: European Commission (Marie Sklodowska-Curie Innovative Training Network “HONOURS”; grant agreement No 721367) to VT and RD (
https://cordis.europa.eu/project/id/721367), The Swiss National Science Foundation (SNSF) grants 179260 to RD (
http://p3.snf.ch/project-179260), 173085 to VT (
http://p3.snf.ch/project-173085), 31CA30_196644 to VT and RD, (
http://p3.snf.ch/project-196644), National Center of Competence in Research (NCCR) on RNA and Disease to VT (
https://nccr-rna-and-disease.ch/), German Federal Ministry of Education and Research (BMBF), grant RAPID (01KI1723A) to VT and RD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.