Viral sequence variation in chronic carriers of hepatitis C virus has a low impact on liver steatosis.: HCV variability and steatosis

Marion Depla 1 Louis D'Alteroche 1, 2 Amélie Le Gouge 3 Alain Moreau 1 Christophe Hourioux 1, 4, 5 Jean-Christophe Meunier 1 Julien Gaillard 5 Anne De Muret 6 Yannick Bacq 2 Farhad Kazemi 7 Aurélie Avargues 3 Emmanuelle Roch 1 Eric Piver 1, 8 Catherine Gaudy-Graffin 1, 9 Bruno Giraudeau 3 Philippe Roingeard 1, 4, 5, *
* Auteur correspondant
1 Virus, pseudo-virus: Morphogénèse et Antigénicité
2 Service de gastro-entérologie
3 CIC - Tours
4 Unité de Biologie Cellulaire
5 ASB - PPF Analyse des Systèmes Biologiques
6 Service d'Anatomie et Cytologie Pathologiques
7 Service d'Hépatogastroentérologie
8 Service de Biochimie
9 Service de Bactériologie-Virologie
Abstract : Most clinical studies suggest that the prevalence and severity of liver steatosis are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in patients infected with other genotypes. This may reflect the diversity and specific intrinsic properties of genotype 3 virus proteins. We analyzed the possible association of particular residues of the HCV core and NS5A proteins known to dysregulate lipid metabolism with steatosis severity in the livers of patients chronically infected with HCV. We used transmission electron microscopy to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were infected with a genotype 3 virus, the other 15 being infected with viruses of other genotypes. We determined the area covered by lipid droplets in liver tissues and analyzed the diversity of the core and NS5A regions encoded by the viral variants circulating in these patients. The area covered by lipid droplets did not differ significantly between patients infected with genotype 3 viruses and those infected with other genotypes. The core and NS5A protein sequences of the viral variants circulating in patients with mild or severe steatosis were evenly distributed throughout the phylogenic trees established from all the collected sequences. Thus, individual host factors seem to play a much greater role than viral factors in the development of severe steatosis in patients chronically infected with HCV, including those infected with genotype 3 viruses.
Keywords : HCV liver steatosis lipid droplet electron microscopy
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Article dans une revue
PLoS ONE, Public Library of Science, 2012, 7 (3), pp.e33749. 〈10.1371/journal.pone.0033749〉
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Marion Depla, Louis D'Alteroche, Amélie Le Gouge, Alain Moreau, Christophe Hourioux, et al.. Viral sequence variation in chronic carriers of hepatitis C virus has a low impact on liver steatosis.: HCV variability and steatosis. PLoS ONE, Public Library of Science, 2012, 7 (3), pp.e33749. 〈10.1371/journal.pone.0033749〉. 〈inserm-00805597〉

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