V'kovski, Philip; Gultom, Mitra; Kelly, Jenna N.; Steiner, Silvio; Russeil, Julie; Mangeat, Bastien; Cora, Elisa; Pezoldt, Joern; Holwerda, Melle; Kratzel, Annika; Laloli, Laura; Wider, Manon; Portmann, Jasmine; Tran, Thao; Ebert, Nadine; Stalder, Hanspeter; Hartmann, Rune; Gardeux, Vincent; Alpern, Daniel; Deplancke, Bart; ... (2021). Disparate temperature-dependent virus-host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium. PLoS biology, 19(3), e3001158. Public Library of Science 10.1371/journal.pbio.3001158
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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 (37°C and 33°C, respectively) have been shown to affect the replication kinetics of several respiratory viruses, as well as host immune response dynamics, we investigated the impact of temperatures during 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 specifically induced by SARS-CoV or SARS-CoV-2, which amplitude was inversely proportional to their replication efficiencies 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.