2. Academic Validation
  3. AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells

AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells

  • Cell Res. 2021 Feb;31(2):126-140. doi: 10.1038/s41422-020-00460-y.
Shuai Wang  # 1 2 3,  Zongyang Qiu  # 1 2 3,  Yingnan Hou  # 1 2 3,  Xiya Deng  # 1 2 3,  Wei Xu  # 4,  Tingting Zheng 1 2 3,  Peihan Wu 1 2 3,  Shaofang Xie 1 2 3,  Weixiang Bian 1 2 3,  Chong Zhang 5,  Zewei Sun 5,  Kunpeng Liu 6,  Chao Shan 6,  Aifu Lin 7,  Shibo Jiang 4,  Youhua Xie 4,  Qiang Zhou 1 2 3,  Lu Lu 8,  Jing Huang 9 10 11,  Xu Li 12 13 14
Affiliations

Affiliations

  • 1 Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China.
  • 2 Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China.
  • 3 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, 310024, China.
  • 4 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai, 200032, China.
  • 5 The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
  • 6 Center for Biosafety Mega-Science, Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China.
  • 7 Key Laboratory for Cell and Gene Engineering of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
  • 8 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai, 200032, China. lul@fudan.edu.cn.
  • 9 Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China. huangjing@westlake.edu.cn.
  • 10 Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China. huangjing@westlake.edu.cn.
  • 11 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, 310024, China. huangjing@westlake.edu.cn.
  • 12 Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China. lixu@westlake.edu.cn.
  • 13 Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China. lixu@westlake.edu.cn.
  • 14 Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, 310024, China. lixu@westlake.edu.cn.
  • # Contributed equally.
PMID: 33420426 DOI: 10.1038/s41422-020-00460-y
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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