Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses.

Abstract

Phosphatidylserine (PS) receptors contribute to two crucial biological processes: apoptotic clearance and entry of many enveloped viruses. In both cases, they recognize PS exposed on the plasma membrane. Here we demonstrate that phosphatidylethanolamine (PE) is also a ligand for PS receptors and that this phospholipid mediates phagocytosis and viral entry. We show that a subset of PS receptors, including T-cell immunoglobulin (Ig) mucin domain protein 1 (TIM1), efficiently bind PE. We further show that PE is present in the virions of flaviviruses and filoviruses, and that the PE-specific cyclic peptide lantibiotic agent Duramycin efficiently inhibits the entry of West Nile, dengue, and Ebola viruses. The inhibitory effect of Duramycin is specific: it inhibits TIM1-mediated, but not L-SIGN-mediated, virus infection, and it does so by blocking virus attachment to TIM1. We further demonstrate that PE is exposed on the surface of apoptotic cells, and promotes their phagocytic uptake by TIM1-expressing cells. Together, our data show that PE plays a key role in TIM1-mediated virus entry, suggest that disrupting PE association with PS receptors is a promising broad-spectrum antiviral strategy, and deepen our understanding of the process by which apoptotic cells are cleared.

• Authors: Audrey Stéphanie Richard, Adam Zhang, Sun-Jin Park, Michael Farzan, Min Zong, Hyeryun Choe
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 47 Pg. 14682-7 (Nov 24 2015) ISSN: 1091-6490 [Electronic] United States
• PMID: 26575624 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Bacteriocins
• HAVCR1 protein, human
• Hepatitis A Virus Cellular Receptor 1
• Ligands
• Membrane Glycoproteins
• Peptides
• Phosphatidylethanolamines
• Receptors, Cell Surface
• Receptors, Virus
• phosphatidylserine receptor
• duramycin
• phosphatidylethanolamine

Topics

• Animals
• Apoptosis (drug effects)
• Bacteriocins (metabolism, pharmacology)
• Dengue (virology)
• Dengue Virus (drug effects, physiology)
• Ebolavirus (drug effects, physiology)
• Hemorrhagic Fever, Ebola (virology)
• Hepatitis A Virus Cellular Receptor 1
• Humans
• Jurkat Cells
• Ligands
• Membrane Glycoproteins (metabolism)
• Membranes (drug effects)
• Mice
• Peptides (metabolism, pharmacology)
• Phagocytosis (drug effects)
• Phosphatidylethanolamines (metabolism)
• Receptors, Cell Surface (metabolism)
• Receptors, Virus (metabolism)
• Virion (metabolism)
• Virus Internalization (drug effects)
• West Nile Fever (virology)
• West Nile virus (drug effects, physiology)