State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, and The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
J Infect. 2020 Oct;81(4):e1-e10. doi: 10.1016/j.jinf.2020.07.016. Epub 2020 Jul 21.
Respiratory and intestinal tract are two primary target organs of SARS-CoV-2 infection. However, detailed characterization of the host-virus interplay in infected human lung and intestinal epithelial cells is lacking.
We utilized immunofluorescence assays, flow cytometry, and RT-qPCR to delineate the virological features and the innate immune response of the host cells against SARS-CoV-2 infection in two prototype human cell lines representing the human lung (Calu3) and intestinal (Caco2) epithelium when compared with SARS-CoV.
Lung epithelial cells were significantly more susceptible to SARS-CoV-2 compared to SARS-CoV. However, SARS-CoV-2 infection induced an attenuated pro-inflammatory cytokines/chemokines induction and type I and type II IFN responses. A single dose of 10 U/mL interferon-β (IFNβ) pretreatment potently protected both Calu3 and Caco2 against SARS-CoV-2 infection. Interestingly, SARS-CoV-2 was more sensitive to the pretreatment with IFNβ and IFN inducer than SARS-CoV in Calu3.
Despite robust infection in both human lung and intestinal epithelial cells, SARS-CoV-2 could attenuate the virus-induced pro-inflammatory response and IFN response. Pre-activation of the type I IFN signaling pathway primed a highly efficient antiviral response in the host against SARS-CoV-2 infection, which could serve as a potential therapeutic and prophylactic maneuver to COVID-19 patients.
呼吸道和肠道是 SARS-CoV-2 感染的两个主要靶器官。然而，对于感染的人肺和肠上皮细胞中宿主-病毒相互作用的详细特征仍缺乏了解。
我们利用免疫荧光分析、流式细胞术和 RT-qPCR 来描绘在与人肺（Calu3）和肠（Caco2）上皮细胞两种原型细胞系中，宿主细胞针对 SARS-CoV-2 感染的病毒学特征和固有免疫反应，并与 SARS-CoV 进行比较。
与 SARS-CoV 相比，肺上皮细胞更容易被 SARS-CoV-2 感染。然而，SARS-CoV-2 感染诱导的促炎细胞因子/趋化因子诱导和 I 型和 II 型 IFN 反应较弱。10 U/mL 干扰素-β（IFNβ）的单次剂量预处理可显著保护 Calu3 和 Caco2 免受 SARS-CoV-2 感染。有趣的是，与 SARS-CoV 相比，SARS-CoV-2 在 Calu3 中对 IFNβ 和 IFN 诱导剂预处理更为敏感。
尽管 SARS-CoV-2 能够在人肺和肠上皮细胞中进行强烈感染，但它可以减弱病毒诱导的促炎反应和 IFN 反应。I 型 IFN 信号通路的预先激活可在宿主中引发针对 SARS-CoV-2 感染的高效抗病毒反应，这可能成为 COVID-19 患者的一种潜在治疗和预防手段。
