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.