title: Subtype mutations in the envelope 2 region including phosphorylation homology domain of hepatitis C virus do not predict effectiveness of antiviral therapy.
abstract: The aim of this study was to determine whether specific sequences of the phosphorylation homology domain (PePHD) region could be correlated with differences in response to antiviral therapy in patients infected with hepatitis C virus subtypes 1b, 2c, 3a and 4c/d. We included 43 patients (22 sustained responders and 21 nonresponders or relapsers) in the study, who were classified according to early viral decline during the first weeks of antiviral treatment and response at end of follow up. Type of mutations, mutation frequency, genetic diversity and phylogenetic relationships were compared at the PePHD and flanking regions. Phylogenetic trees showed that each sequence clustered together with those of the same subtype. Sequences from subtypes 1b and 4c/d resembled more closely the phosphorylation sites of protein kinase R and eIF2 alpha than sequences from genotypes 2c and 3a, the latter with higher response rates to interferon-alpha (IFN alpha) treatment. However, within specific subtypes, no separate clusters of responders and nonresponders were observed either at the beginning or at the end of follow up. We were not able to find any particular sequence or mutation in the PePHD region or in any other subregion of the fragment studied that allowed prediction of treatment response.
authors.affiliation: Liver Unit, Department of Medicine, Hospital Universitari Vall d'Hebron, Barcelona, Spain. jquer@vhebron.es
authors.forename: J
authors.initials: J
authors.lastname: Quer
authors.forename: P
authors.initials: P
authors.lastname: Murillo
authors.forename: M
authors.initials: M
authors.lastname: Martell
authors.forename: J
authors.initials: J
authors.lastname: Gómez
authors.forename: J I
authors.initials: JI
authors.lastname: Esteban
authors.forename: R
authors.initials: R
authors.lastname: Esteban
authors.forename: J
authors.initials: J
authors.lastname: Guardia
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D010802:Phylogeny; D012367:RNA, Viral / Q000737:chemistry; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus