title: [Comparison of 5'UTR and HVR1 of hepatitis c virus (HCV) in serum and peripheral blood mononuclear cells in the early phase of interferon and ribavirin treatment].
abstract: Genetic heterogeneity is a characteristic feature of hepatitis C virus (HCV) and it reflects selection mechanisms affecting the virus. It is considered a major factor contributing the viral persistence and drug resistance. The following work presents the preliminary results of 5'UTR and E2/HVR1 genetic variation analysis and comparison in serum and peripheral blood mononuclear cells (PBMC) of 7 patients before and during the early phase of pegylated interferon alfa (PEG-IFN-alpha) and ribavirin therapy. Single strand conformational polymorphism (SSCP) analysis revealed genetic stability of 5'UTR in all but one patient who did not respond to treatment (SVR-), where new genetic variants appeared. E2/HVR1 genetic changes were characteristic in patients displaying treatment failure (SVR-) and usually reflected fluctuations in complexity and appearance of new genetic HCV variants. Genetic changes (reduction in complexity) were found in one of three sustained virological responders (SVR+ patients). Comparatory analysis of the HCV quasispecies present in serum and PBMC showed differences in at least one analysed region in all non-responders. Presented results suggest the independent forces driving genetic changes in analysed regions. They also point out the presence of genetic compartmentalization possibly having an impact on antiviral treatment result.
authors.affiliation: Zakład Immunopatologii Chorób Zakaźnych i Pasozytniczych, Warszawski Uniwersytet Medyczny. kamila.caraballo@wum.edu.pl
authors.forename: Kamila Caraballo
authors.initials: KC
authors.lastname: Cortés
authors.forename: Iwona
authors.initials: I
authors.lastname: Ośko
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pawełczyk
authors.forename: Hanna
authors.initials: H
authors.lastname: Berak
authors.forename: Maria
authors.initials: M
authors.lastname: Fic
authors.forename: Andrzej
authors.initials: A
authors.lastname: Horban
authors.forename: Marek
authors.initials: M
authors.lastname: Radkowski
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D014644:Genetic Variation; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D011044:Poland; D018807:Polymorphism, Single-Stranded Conformational; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D012254:Ribavirin