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|Title: ||Sterol biosynthesis pathway is part of the interferon host defence response|
|Authors: ||Blanc, Mathieu|
|Supervisor(s): ||Ghazal, Peter|
|Issue Date: ||27-Jun-2011|
|Publisher: ||The University of Edinburgh|
|Abstract: ||Recently, cholesterol metabolism has been shown to modulate the infection of
several viruses and there is growing evidence that inflammatory response to infection
also modulates lipid metabolism.
However little is known about the role of inflammatory processes in modulating lipid
metabolism and their consequences for the viral infection.
This study investigates host-lipid viral interaction pathways using mouse
cytomegalovirus, a large double-stranded DNA genome, which represents one of the
few models for a natural infection of its natural host.
In this study, transcriptomic and lipidomic profiling of macrophages shows that
there is a specific coordinated regulation of the sterol pathways upon viral infection
or treatment with IFNγ or β (but not TNFα, IL1β or IL6) resulting in the decrease of
free cellular cholesterol.
Furthermore, we show that pharmacological and RNAi inhibition of the sterol
pathway augments protection against infection in vitro and in vivo and we identified
that the prenylation branch of the sterol metabolic network was involved in the
Finally, we show that genetic knock out of IFNβ results in a partial reduction while
genetic knock out of Ifnar1 completely abolishes the reduction of the sterol
biosynthetic activity upon infection.
Overall these results support a role for part of the sterol metabolic network in
protective immunity and show that type 1 IFN signalling is both necessary and
sufficient for reducing the sterol metabolic network upon infection; thereby linking
the sterol pathway with IFN defence responses.|
|Sponsor(s): ||British Heart Foundation|
|Appears in Collections:||School of Biomedical Sciences thesis and dissertation collection|
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