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Theses

auto-immunité associée au virus de l'hépatite C: mise en évidence et caractérisation moléculaire d'antigènes cibles

Abstract : The chronic infection by the hepatitis C virus (HCV) can be associated among some patients with extrahepatic auto-immune demonstrations. The question arises concerning the origin of this self-reactivity and of its targets. The stress induced through the chronic infection by the HCV induces the overexpression of HSP70 in hepatic tissues and blood ; this phenomenon is followed by the outbreak of anti-HSP antibodies only among patients having a dysimmunity associated with the HCV. Thanks to a cellular model expressing in a stable way part of the viral polyprotein, we show that, at the cellular level, this viral stress induces not only an increase in the rate of HSP, but also by the apparition of unusual HSP-peptides complexes, endowed with antigenicity. This cellular stress seems to be partly related to the proteolytic activity of the NS3 protease. It is the first time that the direct role of a viral protease in the development of the secondary cellular stress in a viral infection is revealed. NS3 seems to develop a proteolytic activity with respect to several cellular proteins substrates, among them the cytochrome P450 2D6, whose epitopes are implicated in auto-immune hepatitis associated with the HCV. NS3 is thus likely to contribute, through its protease activity, to the emergence of new epitopes. NS3 interaction with C1Inh suggests a possible cellular control of the protease, which could be boosted by the IFN, a cytokine known to increase the synthesis of C1Inh.
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https://tel.archives-ouvertes.fr/tel-00085002
Contributor : Laurence Claveyrolas-Bouillet <>
Submitted on : Tuesday, July 11, 2006 - 12:53:07 PM
Last modification on : Friday, November 6, 2020 - 3:50:08 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 12:01:12 AM

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  • HAL Id : tel-00085002, version 1

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Laurence Claveyrolas-Bouillet. auto-immunité associée au virus de l'hépatite C: mise en évidence et caractérisation moléculaire d'antigènes cibles. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2006. Français. ⟨tel-00085002⟩

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