title: Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein.
abstract: In a bioinformatics-based screen for cellular genes that enhance Zaire ebolavirus (ZEBOV) transduction, AXL mRNA expression strongly correlated with ZEBOV infection. A series of cell lines and primary cells were identified that require Axl for optimal ZEBOV entry. Using one of these cell lines, we identified ZEBOV entry events that are Axl-dependent. Interactions between ZEBOV-GP and the Axl ectodomain were not detected in immunoprecipitations and reduction of surface-expressed Axl by RNAi did not alter ZEBOV-GP binding, providing evidence that Axl does not serve as a receptor for the virus. However, RNAi knock down of Axl reduced ZEBOV pseudovirion internalization and α-Axl antisera inhibited pseudovirion fusion with cellular membranes. Consistent with the importance of Axl for ZEBOV transduction, Axl transiently co-localized on the surface of cells with ZEBOV virus particles and was internalized during virion transduction. In total, these findings indicate that endosomal uptake of filoviruses is facilitated by Axl.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Melinda A
authors.initials: MA
authors.lastname: Brindley
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Hunt
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Kondratowicz
authors.forename: Jill
authors.initials: J
authors.lastname: Bowman
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Sinn
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
authors.forename: Kathrina
authors.initials: K
authors.lastname: Quinn
authors.forename: Melodie L
authors.initials: ML
authors.lastname: Weller
authors.forename: John A
authors.initials: JA
authors.lastname: Chiorini
authors.forename: Wendy
authors.initials: W
authors.lastname: Maury
mesh_terms: D045744:Cell Line, Tumor; D029043:Ebolavirus / Q000235:genetics / Q000502:physiology*; D006023:Glycoproteins; D019142:Hemorrhagic Fever, Ebola / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D006023:Glycoproteins; D011518:Proto-Oncogene Proteins; D014759:Viral Envelope Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase