Loading...
Files
Date
relationships.isAuthorOf
Publisher
Philipps-Universität Marburg
item.page.supervisor-of-thesis
Abstract
In the present work the regulation of apoptosis in Ebolavirus-Zaire
(ZEBOV)-infected cells was analyzed. Studies with infected monkeys revealed
that no apoptosis was detected in ZEBOV-infected cells whereas the number of
lymphocytes, not infected by ZEBOV, decreases strongly during infection by
apoptosis leading to an impairment if the immune reaction. The secretion of
(TNF)-related apoptosis-inducing ligand (TRAIL) from infected cells is in
discussion as determining factor but in the present work a reduction in
TRAIL-mRNA-levels in ZEBOV-infected cells was detected.
Aim of this work was to determine if ZEBOV inhibits the induction of
apoptosis in infected cells. It could be shown that infection with ZEBOV
does not lead to apoptosis in cultured cells and neither activation of
initiator caspases 8 and 9 nor executioner caspase 3 was observed. Infection
with ZEBOV does not change the levels of anti-apoptotic protein Bcl-2 and
pro-apoptotic protein Bax at mRNA- or protein-level, which regulate
apoptosis at the mitochondria.
Subsequently ZEBOV-infected cells were exposed to multiple apoptotic
stimuli, to activate different apoptosis signaling pathways and therefore to
determine a potential inhibitory effect of ZEBOV-infection. However in none
of the performed experiments an inhibition of apoptosis by ZEBOV was
observed. Neither activation of receptor-induced apoptosis by
TRAIL-treatment, nor induction of mitochondrial-dependant apoptosis via
Campthotecin-treatment or infection with Vesicular-Stomatitis-Virus were
inhibited by ZEBOV-infection.
Since inhibition of protein kinase R (PKR) by ZEBOV was already described,
it was analyzed if this leads to inhibition of apoptosis. Although ZEBOV
inhibits activation of PKR induced by infection with Sendaivirus or
transfection of poly-IC, induction of apoptosis was not suppressed. Since it
cannot be ruled out that the used stimuli also induce PKR-independent
apoptosis signaling, the role of PKR inhibition by ZEBOV in apoptosis
regulation could not be clarified definitely.
A number of viruses induce survival signaling like PI3K/ Akt-signaling to
prevent induction of apoptosis. However at no time in ZEBOV-infection
activation of Akt in infected cells was observed. According to this, missing
apoptosis in ZEBOV-infected cells can not be explained by induction of
survival signaling.
Overexpression of the ZEBOV glycoprotein GP in cells leads to induction of
apoptosis, which could not be prevented by infection with ZEBOV. This
suggests that a balanced viral protein expression is critical for prevention
of apoptosis.
In summary it could be assessed that infection with ZEBOV does not lead to
induction of apoptosis but there is as well no inhibition of apoptosis. In
fact it seems that ZEBOV avoids the recognition of pathogenic patterns in
infected cells so that virus defense signaling is not induced.
Review
Metadata
Contributors
Supervisor:
Dates
Created: 2008Issued: 2008-10-08Updated: 2011-08-10
Faculty
Fachbereich Biologie
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
ApoptosisEbola-Virus
DFG-subjects
Ebola-VirusApoptosis
DDC-Numbers
570
show more
Olejnik, Judith: Regulation von Apoptose in Ebolavirus-infizierten Zellen. : Philipps-Universität Marburg 2008-10-08. DOI: https://doi.org/10.17192/z2008.0496.
License
This item has been published with the following license: In Copyright