PMID:21047970

Citation	Hunt, CL, Kolokoltsov, AA, Davey, RA and Maury, W (2011) The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus. J. Virol. 85:334-47
Abstract	Axl, a plasma membrane-associated Tyro3/Axl/Mer (TAM) family member, is necessary for optimal Zaire ebolavirus (ZEBOV) glycoprotein (GP)-dependent entry into some permissive cells but not others. To date, the role of Axl in virion entry is unknown. The focus of this study was to characterize entry pathways that are used for ZEBOV uptake in cells that require Axl for optimal transduction and to define the role of Axl in this process. Through the use of biochemical inhibitors, interfering RNA (RNAi), and dominant negative constructs, we demonstrate that ZEBOV-GP-dependent entry into these cells occurs through multiple uptake pathways, including both clathrin-dependent and caveola/lipid raft-mediated endocytosis. Other dynamin-dependent and -independent pathways such as macropinocytosis that mediate high-molecular-weight dextran uptake also stimulated ZEBOV-GP entry into these cells, and inhibitors that are known to block macropinocytosis inhibited both dextran uptake and ZEBOV infection. These findings provided strong evidence for the importance of this pathway in filovirus entry. Reduction of Axl expression by RNAi treatment resulted in decreased ZEBOV entry via macropinocytosis but had no effect on the clathrin-dependent or caveola/lipid raft-mediated endocytic mechanisms. Our findings demonstrate for the first time that Axl enhances macropinocytosis, thereby increasing productive ZEBOV entry.
Links	PubMed PMC3014168 Online version:10.1128/JVI.01278-09
Keywords	Animals; Cell Line; Cercopithecus aethiops; Clathrin/metabolism; Ebolavirus/genetics; Ebolavirus/metabolism; Ebolavirus/pathogenicity; Endocytosis; Humans; Kidney/cytology; Kidney/virology; Pinocytosis/physiology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/metabolism; Vero Cells; Viral Envelope Proteins/metabolism; Virus Internalization
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:UFO	involved_in	GO:0046718: viral entry into host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:UFO	involved_in	GO:0048549: positive regulation of pinocytosis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:UFO		GO:0046718: entry of virus into host cell	ECO:0000315:		P		Fig. 1	complete CACAO 2431
HUMAN:UFO		GO:0048549: positive regulation of pinocytosis	ECO:0000315:		P		Fig. 7A	complete CACAO 2433
HUMAN:EPS15		GO:0019065: receptor-mediated endocytosis of virus by host	ECO:0000315:		P		Fig. 2B Part of the clathrin-mediated endocytosis entry pathway.	complete CACAO 2434
HUMAN:EPS15	involved_in	GO:0019065: receptor-mediated endocytosis of virus by host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAV1		GO:0019065: receptor-mediated endocytosis of virus by host	ECO:0000316:	UniProtKB:P51636	P		Fig. 2EFG Part of the caveola/lipid raft-mediated entry pathway	complete CACAO 2436
HUMAN:CAV1	involved_in	GO:0019065: receptor-mediated endocytosis of virus by host cell	ECO:0000316: genetic interaction evidence used in manual assertion	UniProtKB:P51636	P		Seeded From UniProt	complete
HUMAN:CAV2		GO:0019065: receptor-mediated endocytosis of virus by host	ECO:0000316:	UniProtKB:O60840	P		Fig. 2EFG Part of the caveola/lipid raft-mediated entry pathway	complete CACAO 2437
HUMAN:CAV2	involved_in	GO:0019065: receptor-mediated endocytosis of virus by host cell	ECO:0000316: genetic interaction evidence used in manual assertion	UniProtKB:O60840	P		Seeded From UniProt	complete

References

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