Scrutiny of human lung infection by SARS-CoV-2 and associated human immune responses in humanized mice
Hu, Z.; Sun, R.; Zhao, Z.; Fu, C.; Wang, Y.; Guo, Z.; Zhang, C.; Liu, L.; Zhang, C.; Shu, C.; He, J.; Li, W.; Zhou, Q.; Gao, Y.; Hua, S.; Yang, Y.-G.
Show abstract
There is an urgent need for animal models of COVID-19 to study immunopathogenesis and test therapeutic intervenes. In this study we showed that NSG mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by 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-seq examination identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, interferon stimulation, and pulmonary fibrosis between HL grafts from infected and control NSG-L mice. Furthermore, when infecting humanized mice with human immune system (HIS) and autologous HL grafts (HISL mice), the 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.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease 93%
- Essential Role of Protein Kinase R in the Pathogenesis of Pulmonary Veno-occlusive Disease 93%
- Impact of cell culture on the transcriptomic programs of primary and iPSC-derived human alveolar type 2 cells 92%
Similar papers in this journal
- Differential Immunoregulation by Human Surfactant Protein A Variants Determines Severity of SARS-CoV-2-induced Lung Disease 94%
- A Novel Humanized Mouse Model for HIV and Tuberculosis Co-infection Studies 93%
- Human Interleukin-4-Dependent Facilitation of Human IgG Production in PBL-NOG-hIL-4-Tg mice 93%
Similar papers in this journal
- Airway epithelial cells and macrophages trigger IL-6-CD95/CD95L axis and mediate initial immunopathology of COVID-19 93%
- Host and microbiome features of secondary infections in lethal covid-19 93%
- Secreted ORF8 is a pathogenic cause of severe Covid-19 and potentially targetable with select NLRP3 inhibitors 93%
Similar papers in this journal
- Evaluation of SARS-CoV-2 Entry, Inflammation and New Therapeutics in Human Lung Tissue Cells 94%
- Pulmonary mesenchymal stem cells are engaged in distinct steps of host response to respiratory syncytial virus infection 94%
- Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression 93%
Similar papers in this journal
- COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis 93%
- Combination therapy with oral antiviral and anti-inflammatory drugs improves the efficacy of delayed treatment in severe COVID-19 92%
- Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.