title: Analysis of genotype 1b hepatitis C virus IRES in serum and peripheral blood mononuclear cells in patients treated with interferon and ribavirin.
abstract: Hepatitis C virus (HCV) highly conserved IRES (internal ribosome entry site) sequence, localized within the 5(')-untranslated region (5(')UTR), may determine viral properties like replication efficiency and cell tropism. The aim of the present study was to characterize newly emerging 5(')UTR variants in serum and peripheral blood mononuclear cells (PBMC) in chronic hepatitis C patients treated with interferon (IFN) and ribavirin and to identify their effect on IRES secondary structures. The study group consisted of 87 patients infected with genotype 1b from whom serum and PBMC samples were collected at 9 time points (before, during, and after treatment). New 5(')UTR variants developed in 9 patients. Out of the overall 14 new variants, 9 (64%) were found in PBMC. HCV variants with decreased thermodynamic stability were identified only in PBMC and C183U mutation was the most common one in this compartment. In conclusion, antiviral treatment may favor emergence of new 5(')UTR variants both in blood and in PBMC compartments. However, variants developing in the latter compartment were predicted to have lower thermodynamic stability of the IRES secondary structures compared to serum strains. C-U change in position 183, which has not been described previously, might indicate viral adaptation to lymphoid cells.
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Bukowska-Ośko
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Caraballo Cortés
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pawełczyk
authors.affiliation: Department of Medical Genetics, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Fic
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Perlejewski
authors.affiliation: Department of Laboratory Medicine and Clinical Immunology of Developmental Age, Medical University of Warsaw, 24 Marszałkowska Street, 00-576 Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Demkow
authors.affiliation: Hospital for Infectious Diseases, 37 Wolska Street, 01-201 Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Berak
authors.affiliation: Hospital for Infectious Diseases, 37 Wolska Street, 01-201 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Laskus
authors.affiliation: Department of Immunopathology of Infectious and Parasitic Diseases, Medical University of Warsaw, 3c Pawińskiego Street, 02-106 Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012367:RNA, Viral / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage*; D056189:Viral Tropism / Q000187:drug effects / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D038621:Regulatory Sequences, Ribonucleic Acid; D012254:Ribavirin