title: Viral sequence variation in chronic carriers of hepatitis C virus has a low impact on liver steatosis.
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.
authors.affiliation: INSERM U966, Université François Rabelais and CHRU de Tours, Tours, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Depla
authors.forename: Louis
authors.initials: L
authors.lastname: d'Alteroche
authors.forename: Amélie
authors.initials: A
authors.lastname: Le Gouge
authors.forename: Alain
authors.initials: A
authors.lastname: Moreau
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourioux
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Meunier
authors.forename: Julien
authors.initials: J
authors.lastname: Gaillard
authors.forename: Anne
authors.initials: A
authors.lastname: de Muret
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bacq
authors.forename: Farhad
authors.initials: F
authors.lastname: Kazemi
authors.forename: Aurélie
authors.initials: A
authors.lastname: Avargues
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Roch
authors.forename: Eric
authors.initials: E
authors.lastname: Piver
authors.forename: Catherine
authors.initials: C
authors.lastname: Gaudy-Graffin
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001706:Biopsy; D017124:Conserved Sequence; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase