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AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells.
- 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.
- Subjects :
- Bronchi cytology
Bronchi metabolism
Cell Line
Humans
Lung cytology
Lung metabolism
Models, Molecular
Protein Interaction Domains and Motifs
Proto-Oncogene Proteins analysis
Receptor Protein-Tyrosine Kinases analysis
Respiratory Mucosa metabolism
SARS-CoV-2 chemistry
Spike Glycoprotein, Coronavirus analysis
Virus Internalization
Axl Receptor Tyrosine Kinase
COVID-19 metabolism
Proto-Oncogene Proteins metabolism
Receptor Protein-Tyrosine Kinases metabolism
Respiratory Mucosa cytology
SARS-CoV-2 physiology
Spike Glycoprotein, Coronavirus metabolism
Subjects
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