The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus

Catherine L Hunt; Andrey A Kolokoltsov; Robert A Davey; Wendy Maury

doi:10.1128/JVI.01278-09

Back

The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus

Journal article

Open access

Peer reviewed

The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus

Catherine L Hunt, Andrey A Kolokoltsov, Robert A Davey and Wendy Maury

Journal of virology, Vol.85(1), pp.334-347

01/2011

DOI: 10.1128/JVI.01278-09

PMCID: PMC3014168

PMID: 21047970

Files and links (1)

url

https://doi.org/10.1128/JVI.01278-09View

Published (Version of record) Open Access

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.

Proto-Oncogene Proteins - metabolism

Cell Line

Ebolavirus - metabolism

Humans

Cercopithecus aethiops

Ebolavirus - pathogenicity

Proto-Oncogene Proteins - genetics

Kidney - cytology

Ebolavirus - genetics

Receptor Protein-Tyrosine Kinases - metabolism

Clathrin - metabolism

Virus Internalization

Endocytosis

Animals

Pinocytosis - physiology

Receptor Protein-Tyrosine Kinases - genetics

Viral Envelope Proteins - metabolism

Kidney - virology

Vero Cells

Details

Title: Subtitle: The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus
Creators: Catherine L Hunt - Dept. Microbiology, University of Iowa, Iowa City, IA 52242, USA
Andrey A Kolokoltsov
Robert A Davey
Wendy Maury
Resource Type: Journal article
Publication Details: Journal of virology, Vol.85(1), pp.334-347
DOI: 10.1128/JVI.01278-09
PMID: 21047970
PMCID: PMC3014168
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Grant note: R21 AI082409 / NIAID NIH HHS AI73306 / NIAID NIH HHS U54 AI057156 / NIAID NIH HHS AI082409 / NIAID NIH HHS AI057156 / NIAID NIH HHS
Language: English
Date published: 01/2011
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083280102771

Metrics

19 Record Views

133 Times Cited - Web of Science