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coexpression of GP with VP40 in mammalian cells produces filamen-
tous virus-like particles decorated with GP spikes (Fig. 4b). 9,17,18
These GP spikes appear to be arranged in a regular order. 9 Mature
Ebola virus GP is also released in the form of spiked virosomes
from cells expressing GP alone; 9,19 however, the arrangement of
these GP spikes seems to be irregular. 9 Such morphological find-
ings suggest an interaction between VP40 and GP, although a
direct interaction has not yet been demonstrated. We also found
efficient incorporation of Marburg virus GP and vesicular stomati-
tis virus glycoprotein into Ebola VP40-induced VLPs. 20 Since the
cytoplasmic tails of these glycoproteins share no sequence similar-
ity, a specific interaction between VP40 and the glycoprotein may
not be required for particle incorporation; rather, cellular compo-
nents, which could exist in lipid raft domains (see below), may link
VP40 to the glycoprotein.
Lipid raft microdomains have been implicated in the assembly and
budding of many viruses. 54 Filovirus GP associates with lipid rafts in
GP-expressing cells and in virus-infected cells. 17 VP40 also localizes to
lipid rafts, predominantly in its oligomeric form. 21 Deletion of the
VP40 carboxy-terminus or replacement of prolines 283 and 286 abol-
ishes raft association but does not affect oligomerization. 21 Both of
these VP40 mutations result in reduced VLP release, which correlates
with the observed decrease in raft association. 21 Thus, raft association
appears necessary for efficient particle production. The released viri-
ons contain the raft-associated glycolipid GM1, 17 but not the raft-
excluded protein transferrin receptor, 17 a finding that implies
filoviruses may use lipid rafts as the final gateway for the exit of
mature virions, similar to the mechanism used by human immunode-
ficiency virus type 1, 22 measles virus, 23 Sendai virus 24 and respiratory
syncytial virus. 25 Although the precise way in which filoviruses use
lipid rafts has yet to be determined, the lipid rafts may serve as build-
ing platforms for filovirus assembly.
Use of Cellular Transport Pathways
To perform their functions in particle assembly and budding, viral
matrix proteins must make use of the cellular transport pathways.
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