title: Nucleotide variability and translation efficiency of the 5' untranslated region of hepatitis A virus: update from clinical isolates associated with mild and severe hepatitis.
abstract: Mutations in the internal ribosome entry site (IRES) of hepatitis A virus (HAV) have been associated with enhanced in vitro replication and viral attenuation in animal models. To address the possible role of IRES variability in clinical presentation, IRES sequences were obtained from HAV isolates associated with benign (n = 8) or severe (n = 4) hepatitis. IRES activity was assessed using a bicistronic dual-luciferase expression system in adenocarcinoma (HeLa) and hepatoma (HuH7) cell lines. Activity was higher in HuH7 than in HeLa cells, except for an infrequently isolated genotype IIA strain. Though globally low, significant variation in IRES-dependent translation efficiency was observed between field isolates, reflecting the low but significant genetic variability of this region (94.2% +/- 0.5% nucleotide identity). No mutation was exclusive of benign or severe hepatitis, and variations in IRES activity were not associated with a clinical phenotype, indirectly supporting the preponderance of host factors in determining the clinical presentation.
authors.affiliation: AP-HP, Hôpital Paul Brousse Centre National de Référence du Virus de l’Hépatite A, Villejuif, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mackiewicz
authors.forename: Anne
authors.initials: A
authors.lastname: Cammas
authors.forename: Delphine
authors.initials: D
authors.lastname: Desbois
authors.forename: Eric
authors.initials: E
authors.lastname: Marchadier
authors.forename: Sandra
authors.initials: S
authors.lastname: Pierredon
authors.forename: Frédérik
authors.initials: F
authors.lastname: Beaulieux
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dussaix
authors.forename: Stephan
authors.initials: S
authors.lastname: Vagner
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Roque-Afonso
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002460:Cell Line; D002648:Child; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005602:France; D014644:Genetic Variation; D005838:Genotype; D006367:HeLa Cells; D006506:Hepatitis A / Q000821:virology*; D030041:Hepatitis A virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral