Hepatitis C virus-mediated mitochondrial dysfunctions are prevented and rescued by cyclophilin inhibition

Details

Serval ID
serval:BIB_99B0ACF253A9
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Hepatitis C virus-mediated mitochondrial dysfunctions are prevented and rescued by cyclophilin inhibition
Title of the conference
36th FEBS Congress of the Biochemistry for Tomorrows Medicine
Author(s)
Capitanio N., Quarato G., Scrima R., Gavillet B., Vuagniaux G., Moradpour D., Piccoli C.
Address
Torino, Italy, June 25-30, 2011
ISBN
1742-464X
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
278
Series
FEBS Journal
Pages
155
Language
english
Notes
Publication type : Meeting Abstract
Abstract
Alisporivir (Debio-025) is an analogue of cyclosporine A andrepresents the prototype of a new class of non-immunosuppressivecyclophilin inhibitors. In vitro and in vivo studies have shownthat alisporivir inhibits hepatitis C virus (HCV) replication andongoing clinical trials are exploring its therapeutic potential inpatients with chronic hepatitis C. Recent data suggest that theantiviral effect is mediated by inhibition of cyclophilin A whichis an essential host factor in the HCV life cycle. However, alisporiviralso inhibits mitochondrial permeability transition by bindingto cyclophilin D. As HCV is known to affect mitochondrialfunction, we explored the effect of alisporivir on HCV proteinmediatedmitochondrial dysfunction. By the use of inducible celllines, which allow to investigate the effects of HCV polyproteinexpression independent from viral RNA replication and whichrecapitulate the major alterations of mitochondrial bioenergeticsobserved in infectious cell systems, we show that alisporivir preventsHCV protein-mediated cytochrome c redistribution,decrease of cell respiration, collapse of mitochondrial membranepotential, overproduction of reactive oxygen species and mitochondrialcalcium overload. Strikingly, some of the HCV-mediatedmitochondrial dysfunctions could even be rescued byalisporivir. These observations provide new insights into thepathogenesis of HCV-related liver disease and reveal an additionalmechanism of action of alisporivir that is likely beneficialin the treatment of chronic hepatitis C.
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Create date
04/10/2011 14:16
Last modification date
20/08/2019 15:01
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