Subject(s)
Bone Marrow/pathology , COVID-19/complications , Death, Sudden/etiology , Diagnostic Errors , Hematoma, Subdural/etiology , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Promyelocytic, Acute/diagnosis , Nuclear Proteins/analysis , SARS-CoV-2/isolation & purification , Biomarkers, Tumor/analysis , COVID-19/blood , DNA-Binding Proteins/analysis , Death, Sudden/pathology , Dioxygenases , Disseminated Intravascular Coagulation/etiology , False Negative Reactions , Fatal Outcome , Humans , Isocitrate Dehydrogenase/analysis , Leukemia, Myeloid, Acute/genetics , Lung/virology , Male , Middle Aged , Nasopharynx/virology , Neutropenia/etiology , Nucleophosmin , Proto-Oncogene Proteins/analysis , Thrombocytopenia/etiologyABSTRACT
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.