Role of the phosphatidylserine receptor TIM-1 in enveloped-virus entry

Sven Moller-Tank; Andrew S Kondratowicz; Robert A Davey; Paul D Rennert; Wendy Maury

doi:10.1128/JVI.01025-13

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Role of the phosphatidylserine receptor TIM-1 in enveloped-virus entry

Journal article

Open access

Peer reviewed

Role of the phosphatidylserine receptor TIM-1 in enveloped-virus entry

Sven Moller-Tank, Andrew S Kondratowicz, Robert A Davey, Paul D Rennert and Wendy Maury

Journal of virology, Vol.87(15), pp.8327-8341

08/2013

DOI: 10.1128/JVI.01025-13

PMCID: PMC3719829

PMID: 23698310

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Abstract

The cell surface receptor T cell immunoglobulin mucin domain 1 (TIM-1) dramatically enhances filovirus infection of epithelial cells. Here, we showed that key phosphatidylserine (PtdSer) binding residues of the TIM-1 IgV domain are critical for Ebola virus (EBOV) entry through direct interaction with PtdSer on the viral envelope. PtdSer liposomes but not phosphatidylcholine liposomes competed with TIM-1 for EBOV pseudovirion binding and transduction. Further, annexin V (AnxV) substituted for the TIM-1 IgV domain, supporting a PtdSer-dependent mechanism. Our findings suggest that TIM-1-dependent uptake of EBOV occurs by apoptotic mimicry. Additionally, TIM-1 enhanced infection of a wide range of enveloped viruses, including alphaviruses and a baculovirus. As further evidence of the critical role of enveloped-virion-associated PtdSer in TIM-1-mediated uptake, TIM-1 enhanced internalization of pseudovirions and virus-like proteins (VLPs) lacking a glycoprotein, providing evidence that TIM-1 and PtdSer-binding receptors can mediate virus uptake independent of a glycoprotein. These results provide evidence for a broad role of TIM-1 as a PtdSer-binding receptor that mediates enveloped-virus uptake. Utilization of PtdSer-binding receptors may explain the wide tropism of many of these viruses and provide new avenues for controlling their virulence.

Alphavirus - chemistry

Cell Line

Transduction, Genetic

Membrane Glycoproteins - metabolism

Receptors, Virus - metabolism

Humans

Phosphatidylserines - metabolism

Receptors, Cell Surface - metabolism

Hepatitis A Virus Cellular Receptor 1

Virus Internalization

Host-Pathogen Interactions

Ebolavirus - chemistry

Annexin A5 - metabolism

Animals

Baculoviridae - chemistry

Alphavirus - physiology

Ebolavirus - physiology

Baculoviridae - physiology

Details

Title: Subtitle: Role of the phosphatidylserine receptor TIM-1 in enveloped-virus entry
Creators: Sven Moller-Tank - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Andrew S Kondratowicz
Robert A Davey
Paul D Rennert
Wendy Maury
Resource Type: Journal article
Publication Details: Journal of virology, Vol.87(15), pp.8327-8341
DOI: 10.1128/JVI.01025-13
PMID: 23698310
PMCID: PMC3719829
ISSN: 0022-538X
eISSN: 1098-5514
Grant note: R01AI063513-07 / NIAID NIH HHS T32AI007533 / NIAID NIH HHS R01 AI063513 / NIAID NIH HHS R01 AI077519 / NIAID NIH HHS R01AI077519 / NIAID NIH HHS T32 AI007533 / NIAID NIH HHS
Language: English
Date published: 08/2013
Academic Unit: Microbiology and Immunology
Record Identifier: 9984083279602771

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