title: Sequence elements correlating with circulating viral load in genotype 1b hepatitis C virus infection.
abstract: The correlation between hepatitis C virus (HCV) genomic sequences and circulating HCV RNA levels was assessed to investigate the genetic elements affecting viral load. The interferon sensitivity-determining region (ISDR) sequence and the serum viral load were strongly correlated in 226 patients examined. Analysis of the entire HCV genome from six patients (three with a high and the others with a low viral load) with similar ISDR sequences identified several candidate residues associated with viral load. The amino acid (aa) sequences of these candidate residues and flanking regions in 67 additional patients revealed that only the residue at aa 962 varied significantly between the HCV patients with low and high serum loads (P=0.042). At this position, alanine was observed more frequently in the patients with a high viral load. In conclusion, our results strongly suggest that serum HCV RNA loads are inversely correlated with amino acid substitutions in the ISDR, and aa 962 was identified as a possible second determinant of serum HCV RNA load.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan 113-8519.
authors.forename: Hideki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Nagayama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Jun
authors.initials: J
authors.lastname: Itakura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Kosei
authors.initials: K
authors.lastname: Hamano
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
authors.forename: Chifumi
authors.initials: C
authors.lastname: Sato
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000595:Amino Acid Sequence; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005814:Genes, Viral / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D007372:Interferons