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2014 ; 289
(48
): 33590-7
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The Ebola virus matrix protein VP40 selectively induces vesiculation from
phosphatidylserine-enriched membranes
#MMPMID25315776
Soni SP
; Stahelin RV
J Biol Chem
2014[Nov]; 289
(48
): 33590-7
PMID25315776
show ga
Ebola virus is from the Filoviridae family of viruses and is one of the most
virulent pathogens known with ? 60% clinical fatality. The Ebola virus negative
sense RNA genome encodes seven proteins including viral matrix protein 40 (VP40),
which is the most abundant protein found in the virions. Within infected cells
VP40 localizes at the inner leaflet of the plasma membrane (PM), binds lipids,
and regulates formation of new virus particles. Expression of VP40 in mammalian
cells is sufficient to form virus-like particles that are nearly
indistinguishable from the authentic virions. However, how VP40 interacts with
the PM and forms virus-like particles is for the most part unknown. To
investigate VP40 lipid specificity in a model of viral egress we employed giant
unilamellar vesicles with different lipid compositions. The results demonstrate
VP40 selectively induces vesiculation from membranes containing
phosphatidylserine (PS) at concentrations of PS that are representative of the PM
inner leaflet content. The formation of intraluminal vesicles was not
significantly detected in the presence of other important PM lipids including
cholesterol and polyvalent phosphoinositides, further demonstrating PS
selectivity. Taken together, these studies suggest that PM phosphatidylserine may
be an important component of Ebola virus budding and that VP40 may be able to
mediate PM scission.