Disparate temperature-dependent virus-host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium.

Philip V’Kovski,Silvio Steiner,Julie Russeil,Volker Thiel,Elisa Cora,Jasmine Portmann,Bastien Mangeat,Hanspeter Stalder,Ronald Dijkman,Laura Laloli,Vincent Gardeux,Annika Kratzel,Melle Holwerda,Joern Pezoldt,Jenna N Kelly,Bart Deplancke,Mitra Gultom,Manon Wider,Nadine Ebert,Daniel Alpern,Rune Hartmann,Thao Thi Phuong Tran

doi:10.1371/journal.pbio.3001158

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.

Highlights

The zoonotic coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei Province, China, in December 2019 and was soon recognized as the etiological agent of Coronavirus Disease 2019 (COVID-19)
To gain further insight into the dynamics of the innate immune responses to SARS-CoV and SARS-CoV-2 infection, we examined the expression levels of the 29 differentially expressed (DE) genes found in cluster 1 of our temporal analysis that were associated with IFN signaling pathways
Using an authentic in vitro model for the human respiratory epithelium, we demonstrate that SARS-CoV-2, in contrast to SARS-CoV, replicated up to 10-fold more efficiently at temperatures encountered in the upper respiratory tract

Summary

Introduction

The zoonotic coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, Hubei Province, China, in December 2019 and was soon recognized as the etiological agent of Coronavirus Disease 2019 (COVID-19). The cell surface receptor ACE2 and the serine protease TMPRSS2 have been shown to serve as entry determinants for both SARS-CoV and SARS-CoV-2 [2,7,8,9], an accumulating body of evidence shows that the 2 viruses exhibit distinct human-to-human transmission dynamics and follow different clinical courses of infection. These differences between SARS-CoV and SARS-CoV-2 strongly suggest the presence of disparate virus–host dynamics during viral infection in the human respiratory epithelium [10,11,12,13,14,15]

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Results

Conclusion