Humanized mice for investigating SARS-CoV-2 lung infection and associated human immune responses

文献类型： 外文期刊

第一作者： Sun, Renren

作者： Sun, Renren;Fu, Cong;Wang, Yixin;Shu, Chang;He, Jin;Yang, Yong-Guang;Hua, Shucheng;Hu, Zheng;Sun, Renren;Fu, Cong;Wang, Yixin;Shu, Chang;He, Jin;Yang, Yong-Guang;Hua, Shucheng;Hu, Zheng;Zhao, Zongzheng;Guo, Zhendong;Zhang, Chunmao;Gao, Yuwei;Wang, Yixin;Hua, Shucheng;Liu, Lina;Zhang, Cheng

作者机构：

关键词： HISL mice; humanized mouse; lung infection; NSG mice; SARS-CoV-2

期刊名称：EUROPEAN JOURNAL OF IMMUNOLOGY （ 影响因子：6.688； 五年影响因子：6.093 ）

ISSN： 0014-2980

年卷期： 2022 年 52 卷 10 期

页码：

收录情况： SCI

摘要： There is an urgent need for animal models of coronavirus disease 2019 to study immunopathogenesis and test therapeutic intervenes. In this study, we showed that NOD/SCID IL2rg(-/-) (NSG) mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-Sequencing identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, IFN stimulation and pulmonary fibrosis, between HL grafts from infected and control NSG-L mice. Furthermore, when infected with SARS-CoV-2, humanized mice with both human immune system (HIS) and autologous HL grafts (HISL mice) had bodyweight loss and hemorrhage and immune cell infiltration in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live virus at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies.

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