Studies thread: Ebola VP40 & Dendritic Cell Activation

[Vibrant62]

Ebola virus-like particle-induced activation of NF- κ B and Erk signaling in
human dendritic cells requires the glycoprotein mucin domain

http://ac.els-cdn.com/S004268220700...t=1414611862_5df3f7b316c1c5165a6701c51dead093

Virology 364 (2007) 342 ? 354

Abstract
Dendritic cells (DCs), important early targets of Ebola virus (EBOV) infection in vivo, are activated by Ebola virus-like particles (VLPs). To
better understand this phenomenon, we have systematically assessed the response of DCs to VLPs of different compositions. VLPs containing the
viral matrix protein (VP40) and the viral glycoprotein (GP), were found to induce a proinflammatory response highly similar to a prototypical DC
activator, LPS. This response included the production of several proinflammatory cytokines, activation of numerous transcription factors including
NF-kappaB, the functional importance of which was demonstrated by employing inhibitors of NF-kappaB activation, and activation of ERK1/2
MAP kinase. In contrast, VLPs constituted with a mutant GP lacking the heavily glycosylated mucin domain showed impaired NF-kappaB and
Erk activation and induced less DC cytokine production. We conclude that the GP mucin domain is required for VLPs to stimulate human
dendritic cells through NF-kappaB and MAPK signaling pathways.

 

[Vibrant62]

Re: Studies thread: Ebola VP40 & Dendritic Cell Activation

In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding

http://www.pnas.org/content/100/26/15936.full.pdf#page=1&view=FitH

15936?15941
PNAS
December 23, 2003
vol. 100
no. 26

The matrix protein VP40 plays a critical role in Ebola virus assembly
and budding, a process that utilizes specialized membrane domains
known as lipid rafts. Previous studies with purified protein suggest
a role for oligomerization of VP40 in this process. Here, we
demonstrate VP40 oligomers in lipid rafts of mammalian cells,
virus-like particles, and in the authentic Ebola virus. By mutagen-
esis, we identify several critical C-terminal sequences that regulate
oligomerization at the plasma membrane, association with deter-
gent-resistant membranes, and vesicular release of VP40, directly
linking these phenomena. Furthermore, we demonstrate the active
recruitment of TSG101 into lipid rafts by VP40. We also report the
successful application of the biarsenic fluorophore, FlAsH, com-
bined with a tetracysteine tag for imaging of Ebola VP40 in live
cells.