PMID:23297401

Citation	Adu-Gyamfi, E, Soni, SP, Xue, Y, Digman, MA, Gratton, E and Stahelin, RV (2013) The Ebola virus matrix protein penetrates into the plasma membrane: a key step in viral protein 40 (VP40) oligomerization and viral egress. J. Biol. Chem. 288:5779-89
Abstract	Ebola, a fatal virus in humans and non-human primates, has no Food and Drug Administration-approved vaccines or therapeutics. The virus from the Filoviridae family causes hemorrhagic fever, which rapidly progresses and in some cases has a fatality rate near 90%. The Ebola genome encodes seven genes, the most abundantly expressed of which is viral protein 40 (VP40), the major Ebola matrix protein that regulates assembly and egress of the virus. It is well established that VP40 assembles on the inner leaflet of the plasma membrane; however, the mechanistic details of plasma membrane association by VP40 are not well understood. In this study, we used an array of biophysical experiments and cellular assays along with mutagenesis of VP40 to investigate the role of membrane penetration in VP40 assembly and egress. Here we demonstrate that VP40 is able to penetrate specifically into the plasma membrane through an interface enriched in hydrophobic residues in its C-terminal domain. Mutagenesis of this hydrophobic region consisting of Leu(213), Ile(293), Leu(295), and Val(298) demonstrated that membrane penetration is critical to plasma membrane localization, VP40 oligomerization, and viral particle egress. Taken together, VP40 membrane penetration is an important step in the plasma membrane localization of the matrix protein where oligomerization and budding are defective in the absence of key hydrophobic interactions with the membrane.
Links	PubMed PMC3581432 Online version:10.1074/jbc.M112.443960
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
EBOZM:VP40	part_of	GO:0044385: integral to membrane of host cell	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete
EBOZM:VP40	involved_in	GO:0075733: intracellular transport of virus	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
EBOZM:VP40		GO:0046788: egress of virus within host cell	ECO:0000315:		P		Figure 8	complete CACAO 8554
EBOZM:VP40		GO:0019076: viral release from host cell	ECO:0000315:		P		Figure 2B, 2C show that when certain key amino acids are mutated (L213A, L295A, V298A) they do not induce the same amount of surface pressure into the plasma membrane as compared to WT	complete CACAO 8653
EBOZM:VP40		GO:0044385: integral to membrane of host cell	ECO:0000315:		C		Figure 3	complete CACAO 8654
EBOZM:VP40		GO:0020002: host cell plasma membrane	ECO:0000315:		C		Figure 8: Western blots of cells transfected with WT VP40 and several hydrophobic mutants demonstrate that C-terminal domain plasma membrane penetration is critical for viral egress.	complete CACAO 9138

References

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