Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry
| Autor: | Wendy Maury, Robert A. Davey, Andrew S. Kondratowicz, Sven Moller-Tank, Paul D. Rennert |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
viruses
Immunology Receptors Cell Surface Alphavirus Phosphatidylserines medicine.disease_cause Microbiology Cell Line Hepatitis A Virus Cellular Receptor 1 chemistry.chemical_compound Pseudovirion Viral envelope Transduction Genetic Cell surface receptor Virology medicine Animals Humans Annexin A5 Membrane Glycoproteins Ebola virus biology Phosphatidylserine Virus Internalization Ebolavirus biology.organism_classification Virus-Cell Interactions Cell biology chemistry Insect Science Host-Pathogen Interactions Receptors Virus Baculoviridae |
| Zdroj: | Journal of Virology. 87:8327-8341 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01025-13 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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