Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein

Melinda A Brindley; Catherine L Hunt; Andrew S Kondratowicz; Jill Bowman; Patrick L Sinn; Paul B McCray; Kathrina Quinn; Melodie L Weller; John A Chiorini; Wendy Maury

doi:10.1016/j.virol.2011.04.002

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Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein

Journal article

Open access

Peer reviewed

Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein

Melinda A Brindley, Catherine L Hunt, Andrew S Kondratowicz, Jill Bowman, Patrick L Sinn, Paul B McCray, Kathrina Quinn, Melodie L Weller, John A Chiorini and Wendy Maury

Virology (New York, N.Y.), Vol.415(2), pp.83-94

2011

DOI: 10.1016/j.virol.2011.04.002

PMCID: PMC3107944

PMID: 21529875

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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.

Ebolavirus

Filovirus

Tyrosine kinase receptors

Axl

Virus entry

Marburgvirus

Details

Title: Subtitle: Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein
Creators: Melinda A Brindley - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Catherine L Hunt - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Andrew S Kondratowicz - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Jill Bowman - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Patrick L Sinn - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Paul B McCray - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Kathrina Quinn - Molecular Physiology and Therapeutics Branch, National Dental and Craniofacial Research Branch, National Institutes of Health, Bethesda, MD 20892, USA
Melodie L Weller - Molecular Physiology and Therapeutics Branch, National Dental and Craniofacial Research Branch, National Institutes of Health, Bethesda, MD 20892, USA
John A Chiorini - Molecular Physiology and Therapeutics Branch, National Dental and Craniofacial Research Branch, National Institutes of Health, Bethesda, MD 20892, USA
Wendy Maury - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Virology (New York, N.Y.), Vol.415(2), pp.83-94
DOI: 10.1016/j.virol.2011.04.002
PMID: 21529875
PMCID: PMC3107944
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: Elsevier Inc
Grant note: name: NIH, award: AI064526, AI073330; name: NIH, award: HL075363; name: NIH NIAID; DOI: 10.13039/100000072, name: NIH NIDCR; name: NIH, award: T32 A1007533
Language: English
Date published: 2011
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984083284902771

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