title: Genetic evolution of GB virus C/hepatitis G virus (GBV-C/HGV) under interferon pressure.
abstract: The epidemiology and clinical features of chronic GBV-C/HGV infection have largely been explored, but there is little information about the mechanisms enabling GBV-C/HGV to cause persistent infection. Since analysis of the genomic variation of GBV-C/HGV under interferon pressure might provide some insight into this issue, we analyzed the nucleotide sequence variation of the 5'NC and NS3 regions in GBV-C/HGV isolates obtained sequentially from seven patients co-infected with HCV and treated with interferon. A reduction of GBV-C/HGV-RNA serum level below the detection limit of the RT-PCR assay was observed during treatment in all patients, but upon interferon withdrawal, viral RNA remained undetectable in only two patients. Among the five patients who did not clear GBV-C/HGV-RNA, viral strains emerging after treatment were identical to those present at baseline in three cases. In a further case, in whom GBV-C/HGV-RNA re-emerged during therapy (breakthrough episode), several mutations appeared in relapse samples. In the remaining patient, with a mixed infection before therapy, only one of the two GBV-C/HGV strains present at baseline was detected upon treatment withdrawal. These data raise the possibility that positive selection may act over GBV-C/HGV genome during interferon therapy, and contribute to persistence of infection with this virus.
authors.affiliation: Liver Unit, Department of Medicine, Institut d'Investigacions Biomèdiques August Pí i Sunyer (IDIBAPS), Hospital Clinic, Facultad de Medicina, Universidad de Barcelona, Villaroel 170, 08036, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Giménez-Barcons
authors.forename: A
authors.initials: A
authors.lastname: Sánchez-Fueyo
authors.forename: S
authors.initials: S
authors.lastname: Ampurdanés
authors.forename: F
authors.initials: F
authors.lastname: Puig-Basagoiti
authors.forename: M
authors.initials: M
authors.lastname: Guilera
authors.forename: A
authors.initials: A
authors.lastname: Ibáñez
authors.forename: B
authors.initials: B
authors.lastname: Clotet
authors.forename: M A
authors.initials: MA
authors.lastname: Martínez
authors.forename: J
authors.initials: J
authors.lastname: Rodés
authors.forename: J C
authors.initials: JC
authors.lastname: Saiz
authors.forename: J M
authors.initials: JM
authors.lastname: Sánchez-Tapias
mesh_terms: D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D018067:Flaviviridae / Q000235:genetics*; D016679:Genome, Viral; D006521:Hepatitis, Chronic / Q000188:drug therapy* / Q000821:virology*; D006525:Hepatitis, Viral, Human / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins; D012641:Selection, Genetic; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins