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PMID:21529875

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Citation

Brindley, MA, Hunt, CL, Kondratowicz, AS, Bowman, J, Sinn, PL, McCray, PB Jr, Quinn, K, Weller, ML, Chiorini, JA and Maury, W (2011) Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein. Virology 415:83-94

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.

Links

PubMed PMC3107944 Online version:10.1016/j.virol.2011.04.002

Keywords

Cell Line, Tumor; Ebolavirus/genetics; Ebolavirus/physiology; Glycoproteins; Hemorrhagic Fever, Ebola/enzymology; Hemorrhagic Fever, Ebola/genetics; Hemorrhagic Fever, Ebola/metabolism; Hemorrhagic Fever, Ebola/virology; Humans; Protein Binding; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/metabolism; Viral Envelope Proteins/genetics; Viral Envelope Proteins/metabolism; Virus Internalization

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:UFO

part_of

GO:0044228: host cell surface

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:UFO

GO:0044228: host cell surface

ECO:0000314:

C

Fig. 7 and Fig. 8

complete
CACAO 2202


See also

References

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