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

Autor: Bohan D; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Ert HV; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Ruggio N; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Rogers KJ; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Badreddine M; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Aguilar Briseño JA; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Rojas Chavez RA; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Gao B; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX., Stokowy T; Department of Biomedicine, University of Bergen, Bergen Norway., Christakou E; Department of Biomedicine, University of Bergen, Bergen Norway.; BerGenBio ASA, Bergen, Norway., Micklem D; BerGenBio ASA, Bergen, Norway., Gausdal G; BerGenBio ASA, Bergen, Norway., Haim H; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA., Minna J; Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX., Lorens JB; Department of Biomedicine, University of Bergen, Bergen Norway., Maury W; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Jun 24. Date of Electronic Publication: 2021 Jun 24.
DOI: 10.1101/2021.06.15.448419
Abstrakt: 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.
Databáze: MEDLINE