Phosphatidylserine Receptors Enhance SARS-CoV-2 Infection: AXL as a Therapeutic Target for COVID-19

作者：Dana Bohan, Hanora Van Ert, Natalie Ruggio, Kai J. Rogers, Mohammad Badreddine, José A. Aguilar-Briseño, Roberth Anthony Rojas Chávez, Boning Gao, Tomasz Stokowy, Eleni Christakou, David Micklem, Gro Gausdal, Hillel Haim, John D. Minna, James B. Lorens, Wendy Maury · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2021 · DOI：10.1101/2021.06.15.448419 · 被引用次数：16 · 研究领域：Phagocytosis and Immune Regulation、SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies

Phosphatidylserine (PS) receptors are PS binding proteins that mediate uptake of apoptotic bodies. Many enveloped viruses utilize this PS/PS receptor mechanism to adhere to and internalize into the endosomal compartment of cells and this is termed apoptotic mimicry. For viruses that have a mechanism(s) of endosomal escape, apoptotic mimicry is a productive route of virus entry. We evaluated if PS receptors serve as cell surface receptors for SARS-CoV-2 and found that the PS receptors, AXL, TIM-1 and TIM-4, facilitated virus infection when low concentrations of the SARS-CoV-2 cognate receptor, ACE2, was present. Consistent with the established mechanism of PS receptor utilization by other viruses, PS liposomes competed with SARS-CoV-2 for binding and entry. We demonstrated that this PS receptor enhances SARS-CoV-2 binding to and infection of an array of human lung cell lines and is an under-appreciated but potentially important host factor facilitating SARS-CoV-2 entry.