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

[tetano]

Cell Res


. 2021 Jan 8.
doi: 10.1038/s41422-020-00460-y. Online ahead of print.
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 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

• 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.