Genetic evolution of GB virus C/hepatitis G virus (GBV-C/HGV) under interferon pressure.
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.
Giménez-Barcons
M
M
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.
Sánchez-Fueyo
A
A
Ampurdanés
S
S
Puig-Basagoiti
F
F
Guilera
M
M
Ibáñez
A
A
Clotet
B
B
Martínez
M A
MA
Rodés
J
J
Saiz
J C
JC
Sánchez-Tapias
J M
JM
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
D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins