Volume 31, No 2, Feb 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 2, February 2021: 126-140   |  Open Access

ORIGINAL ARTICLES

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

Shuai Wang^1,2,3 , Zongyang Qiu^1,2,3 , Yingnan Hou^1,2,3 , Xiya Deng^1,2,3 , Wei Xu⁴ , Tingting Zheng^1,2,3 , Peihan Wu^1,2,3 , Shaofang Xie^1,2,3 , Weixiang Bian^1,2,3 , Chong Zhang⁵ , Zewei Sun⁵ , Kunpeng Liu⁶ , Chao Shan⁶ , Aifu Lin⁷ , Shibo Jiang⁴ , Youhua Xie⁴ , Qiang Zhou^1,2,3 , Lu Lu^4,* , Jing Huang^1,2,3,* , Xu Li^1,2,3,*

¹Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China
²Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China
³Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang 310024, China
⁴Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Fudan University, Shanghai 200032, China
⁵The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China
⁶Center for Biosafety Mega-Science, Wuhan Institute of Virology, State Key Laboratory of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China
⁷Key Laboratory for Cell and Gene Engineering of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China
These authors contributed equally: Shuai Wang, Zongyang Qiu, Yingnan Hou, Xiya Deng, Wei Xu Correspondence: Lu Lu(lul@fudan.edu.cn)Jing Huang(huangjing@westlake.edu.cn)Xu Li(lixu@westlake.edu.cn)

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.

https://doi.org/10.1038/s41422-020-00460-y

FULL TEXT | PDF

Browse 817