Roles of antiviral sensing and type I interferon signaling in the restriction of SARS-CoV-2 replication

抗病毒感应和 I 型干扰素信号在限制 SARS-CoV-2 复制中的作用

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作者:Elizabeth Geerling, Amanda N Pinski, Taylor E Stone, Richard J DiPaolo, Michael Z Zulu, Kevin J Maroney, James D Brien, Ilhem Messaoudi, Amelia K Pinto

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019. Few studies have compared replication dynamics and host responses to SARS-CoV-2 in cell lines from different tissues and species. Therefore, we investigated the role of tissue type and antiviral genes during SARS-CoV-2 infection in nonhuman primate (kidney) and human (liver, respiratory epithelial, gastric) cell lines. We report different viral growth kinetics and release among the cell lines despite comparable ACE2 expression. Transcriptomics revealed that absence of STAT1 in nonhuman primate cells appeared to enhance inflammatory responses without effecting infectious viral titer. Deletion of RL-6 in respiratory epithelial cells increased viral replication. Impaired infectious virus release was detected in Huh7 but not Huh7.5 cells, suggesting a role for RIG1. Gastric cells MKN45 exhibited robust antiviral gene expression and supported viral replication. Data here provide insight into molecular pathogenesis of and alternative cell lines for studying SARS-CoV-2 infection.

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