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

Authors :
Wang S
Qiu Z
Hou Y
Deng X
Xu W
Zheng T
Wu P
Xie S
Bian W
Zhang C
Sun Z
Liu K
Shan C
Lin A
Jiang S
Xie Y
Zhou Q
Lu L
Huang J
Li X
Source :
Cell research [Cell Res] 2021 Feb; Vol. 31 (2), pp. 126-140. Date of Electronic Publication: 2021 Jan 08.
Publication Year :
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.

Details

Language :
English
ISSN :
1748-7838
Volume :
31
Issue :
2
Database :
MEDLINE
Journal :
Cell research
Publication Type :
Academic Journal
Accession number :
33420426
Full Text :
https://doi.org/10.1038/s41422-020-00460-y