The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Gut Année : 2007

The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model.

Résumé

Background and aims: The prevalence and severity of liver steatosis are higher in patients infected with genotype 3 hepatitis C virus (HCV) than in patients infected with other genotypes. HCV core protein is known to affect lipid metabolism, inducing lipid droplet accumulation both in vitro and in vivo. We used an in vitro cellular model to investigate whether an HCV core protein with residues specific to genotype 3 increased this phenomenon. Methods: Sequence comparisons for HCV core protein domain II, which is known to interact with lipid droplets, identified the phenylalanine (F) residue at position 164 as the only residue specific to genotype 3. We compared the area covered by lipid droplets in sections of cells producing a wild-type genotype 1a HCV core protein with that in cells producing a Y164F mutant protein. Results: Cumulative lipid droplet area was significantly greater in sections of cells producing the Y164F mutant HCV core protein than in cells producing the wild-type protein (p<0.001). The frequency of cell sections containing more than 3 μm2 of lipid droplets, in particular, was higher for the mutant than for the wild-type protein. Conclusion: Our data provide a molecular explanation for HCV genotype 3-specific lipid accumulation. This difference between genotypes may be due to phenylalanine having a higher affinity for lipids than tyrosine (Y). These observations provide useful information for further studies of the mechanisms involved in HCV-induced steatosis.
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Dates et versions

inserm-00167783 , version 1 (23-08-2007)

Identifiants

  • HAL Id : inserm-00167783 , version 1
  • PUBMED : 17213339

Citer

Christophe Hourioux, Romuald Patient, Aurélie Morin, Emmanuelle Blanchard, Moreau Alain, et al.. The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model.: HCV genotype 3-specific steatosis. Gut, 2007, 56 (9), pp.1302-8. ⟨inserm-00167783⟩

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