《Nature,8月6日,Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells》

  • 来源专题:COVID-19科研动态监测
  • 编译者: zhangmin
  • 发布时间:2020-08-18
  • Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells
    Na Zhu, Wenling Wang, Zhidong Liu, Chaoyang Liang, Wen Wang, Fei Ye, Baoying Huang, Li Zhao, Huijuan Wang, Weimin Zhou, Yao Deng, Longfei Mao, Chongyu Su, Guangliang Qiang, Taijiao Jiang, Jincun Zhao, Guizhen Wu, Jingdong Song & Wenjie Tan
    Nature Communications volume 11, Article number: 3910 (2020)

    Abstract
    SARS-CoV-2, a β-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.

  • 原文来源:https://www.nature.com/articles/s41467-020-17796-z
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    • 来源专题:COVID-19科研动态监测
    • 编译者:zhangmin
    • 发布时间:2021-02-04
    • AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells Shuai Wang, Zongyang Qiu, Yingnan Hou, Xiya Deng, Wei Xu, Tingting Zheng, Peihan Wu, Shaofang Xie, Weixiang Bian, Chong Zhang, Zewei Sun, Kunpeng Liu, Chao Shan, Aifu Lin, Shibo Jiang, Youhua Xie, Qiang Zhou, Lu Lu, Jing Huang & Xu Li Cell Research volume 31, pages126–140(2021) Abstract The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.
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    • 来源专题:COVID-19科研动态监测
    • 编译者:xuwenwhlib
    • 发布时间:2020-06-22
    • Transcriptional response of signalling pathways to SARS-CoV-2 infection in normal human bronchial epithelial cells View ORCID ProfileEnes Ak, View ORCID ProfilePinar Pir doi: https://doi.org/10.1101/2020.06.20.163006 Abstract SARS-CoV-2 virus, the pathogen that causes Covid-19 disease, emerged in Wuhan region in China in 2019, infected more than 4M people and is responsible for death of at least 300K patients globally as of May 2020. Identification of the cellular response mechanisms to viral infection by SARS-CoV-2 may shed light on progress of the disease, indicate potential drug targets, and make design of new test methods possible. In this study, we analysed transcriptomic response of normal human bronchial epithelial cells (NHBE) to SARS-CoV-2 infection and compared the response to H1N1 infection. Comparison of transcriptome of NHBE cells 24 hours after mock-infection and SARS-CoV-2 infection demonstrated that most genes that respond to infection were upregulated (320 genes) rather than being downregulated (115 genes). While upregulated genes were enriched in signalling pathways related to virus response, downregulated genes are related to kidney development. We mapped the upregulated genes on KEGG pathways to identify the mechanisms that mediate the response. We identified canonical NFκB, TNF and IL-17 pathways to be significantly upregulated and to converge to NFκB pathway via positive feedback loops. Although virus entry protein ACE2 has low expression in NHBE cells, pathogen response pathways are strongly activated within 24 hours of infection. Our results also indicate that immune response system is activated at the early stage of the infection and orchestrated by a crosstalk of signalling pathways. Finally, we compared transcriptomic SARS-CoV-2 response to H1N1 response in NHBE cells to elucidate the virus specificity of the response and virus specific extracellular proteins expressed by NHBE cells.