SARS-CoV-2 在人体肠道中诱导更强的先天免疫反应，复制效率低于 SARS-CoV：一项对 COVID-19 发病机制具有启示意义的离体研究。
SARS-CoV-2 Induces a More Robust Innate Immune Response and Replicates Less Efficiently Than SARS-CoV in the Human Intestines: An Ex Vivo Study With Implications on Pathogenesis of COVID-19.
机构信息
State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.
出版信息
Cell Mol Gastroenterol Hepatol. 2021;11(3):771-781. doi: 10.1016/j.jcmgh.2020.09.017. Epub 2020 Oct 1.
BACKGROUND AND AIMS
Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile.
METHODS
Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines.
RESULTS
SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues.
CONCLUSION
Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.
背景与目的
除了明显的呼吸道受累外，COVID-19 患者还常出现胃肠道表现。我们比较了 SARS-CoV-2 和 SARS-CoV 对离体人肠组织的感染，以了解它们的复制动力学和免疫激活特征。
方法
从正在玛丽皇后医院进行手术的患者中获取人肠组织。手术切除后，立即对组织进行处理并感染 SARS-CoV-2 或 SARS-CoV。通过免疫组织化学、qRT-PCR 和噬斑分析来确定复制动力学。通过检测干扰素和代表性促炎细胞因子和趋化因子的基因表达来评估感染肠组织中的免疫激活。
结果
SARS-CoV-2 可以感染离体人肠组织并进行有效复制，释放有感染性的病毒颗粒，但不能感染离体人肝和肾组织。重要的是，SARS-CoV-2 的复制效率低于 SARS-CoV，在人肠上皮细胞中引起的细胞病变较少，并且在人肠组织中诱导的先天免疫反应比 SARS-CoV 更强烈，包括 I 型和 III 型干扰素的激活。
结论
使用离体人肠组织作为生理相关模型，我们的数据表明 SARS-CoV-2 可以在人体肠道中有效复制，并提示胃肠道可能是病毒传播的另一种途径。SARS-CoV-2 的复制效率低于 SARS-CoV，与 COVID-19 和 SARS 的临床观察结果一致，这可能是 SARS-CoV-2 在人肠中诱导的免疫激活比 SARS-CoV 更强烈的结果。
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