Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, P.R. China.
Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Cell Rep. 2021 Jan 12;34(2):108628. doi: 10.1016/j.celrep.2020.108628.
Recent studies have profiled the innate immune signatures in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and suggest that cellular responses to viral challenge may affect disease severity. Yet the molecular events that underlie cellular recognition and response to SARS-CoV-2 infection remain to be elucidated. Here, we find that SARS-CoV-2 replication induces a delayed interferon (IFN) response in lung epithelial cells. By screening 16 putative sensors involved in sensing of RNA virus infection, we found that MDA5 and LGP2 primarily regulate IFN induction in response to SARS-CoV-2 infection. Further analyses revealed that viral intermediates specifically activate the IFN response through MDA5-mediated sensing. Additionally, we find that IRF3, IRF5, and NF-κB/p65 are the key transcription factors regulating the IFN response during SARS-CoV-2 infection. In summary, these findings provide critical insights into the molecular basis of the innate immune recognition and signaling response to SARS-CoV-2.
最近的研究描绘了感染严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的患者的固有免疫特征，并表明细胞对病毒挑战的反应可能影响疾病的严重程度。然而，细胞识别和对 SARS-CoV-2 感染的反应的分子事件仍有待阐明。在这里，我们发现 SARS-CoV-2 复制诱导肺上皮细胞中干扰素（IFN）反应的延迟。通过筛选 16 种参与 RNA 病毒感染检测的假定传感器，我们发现 MDA5 和 LGP2 主要调节 SARS-CoV-2 感染时 IFN 的诱导。进一步的分析表明，病毒中间体通过 MDA5 介导的感应特异性激活 IFN 反应。此外，我们发现 IRF3、IRF5 和 NF-κB/p65 是调节 SARS-CoV-2 感染期间 IFN 反应的关键转录因子。总之，这些发现为 SARS-CoV-2 的固有免疫识别和信号转导反应的分子基础提供了重要的见解。
