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Friday, 07/03/2015 8:20:14 AM

Friday, July 03, 2015 8:20:14 AM

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Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of the Ebola Virus.
Adu-Gyamfi E1, Johnson KA1, Fraser ME2, Scott JL1, Soni SP2, Jones KR2, Digman MA3, Gratton E4, Tessier CR5, Stahelin RV6.
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1Department of Chemistry and Biochemistry, the Eck Institute for Global Health, and the Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, 46556.
2Department of Biochemistry and Molecular Biology.
3Department of Biomedical Engineering, University of California, Irvine, California, 92687. Department of Medical and Molecular Genetics, Indiana University School of Medicine-South Bend, South Bend, Indiana 46617.
4Department of Biomedical Engineering, University of California, Irvine, California, 92687.
5Centre for Bioactive Discovery in Health and Ageing, School of Science and Technology, University of New England, Armidale, Australia.
6Department of Chemistry and Biochemistry, the Eck Institute for Global Health, and the Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, Indiana, 46556. Department of Biochemistry and Molecular Biology rstaheli@iu.edu.

Abstract
Lipid enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. The Ebola virus, which buds from the plasma membrane of the host cell causes viral hemorrhagic fever and has a high fatality rate. To date little is known about how budding and egress of the Ebola virus is mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of the Ebola virus matrix protein VP40. VP40 binds PS containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress; whereas PS is typically only on the inner leaflet. Together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus like particles.
IMPORTANCE:
The lipid-enveloped Ebola virus causes severe infection, has a high mortality rate, and currently lacks FDA approved therapeutics or vaccines. The Ebola virus harbors just seven genes in its genome and during the replication process there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell it infects. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This study, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26136573 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/26136573?dopt=Abstract
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