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

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.

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）是2019冠状病毒病的致病原。目前鲜有研究针对不同组织、不同物种来源的细胞系，对比其感染SARS-CoV-2后的病毒复制动力学与宿主应答反应。为此，本研究选取非人灵长类（肾脏）及人类（肝脏、呼吸道上皮、胃组织）来源的细胞系，探究组织类型与抗病毒基因在SARS-CoV-2感染过程中的作用。本研究发现，尽管各细胞系的血管紧张素转换酶2（ACE2）表达水平相当，但其病毒增殖动力学与病毒释放模式均存在显著差异。转录组学分析显示，非人灵长类细胞中STAT1的缺失可增强炎症应答，但不影响感染性病毒滴度。呼吸道上皮细胞中RL-6的缺失可促进病毒复制。研究在Huh7细胞中检测到感染性病毒释放受损，但在Huh7.5细胞中未观察到此现象，提示RIG1参与了该过程。胃组织细胞MKN45可呈现强烈的抗病毒基因表达，并支持病毒复制。本研究数据为SARS-CoV-2感染的分子致病机制研究提供了新视角，同时也为该病毒感染的相关研究提供了可选的细胞系模型。