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Heterogeneity in E2 region of GBV-C/hepatitis G virus and hepatitis C virus
1Second Department of Medicine, Nagoya City University Medical School, Mizuho, Nagoya, Japan.
Insights
GB virus C/hepatitis G virus (GBV-C/HGV) shows less genetic diversity than hepatitis C virus (HCV). GBV-C/HGV strains exhibit varied responses to interferon-alpha (IFN) therapy.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Hepatitis C virus (HCV) exhibits quasispecies nature and possesses a hypervariable region (HVR).
- GB virus C/hepatitis G virus (GBV-C/HGV), though related to HCV, has an uncharacterized population heterogeneity and antigenic variation.
- Understanding GBV-C/HGV heterogeneity is crucial for comprehending its in vivo behavior and therapeutic responses.
Purpose of the Study:
- To investigate and compare the viral heterogeneity and population dynamics of GBV-C/HGV and HCV in patients with concomitant infections.
- To evaluate the impact of interferon-alpha (IFN) therapy on GBV-C/HGV quasispecies.
- To assess the antigenic stability and genetic diversity of GBV-C/HGV in comparison to HCV.
Main Methods:
- Single-strand conformation polymorphism (SSCP) analysis was employed to examine viral heterogeneity in six coinfected patients.
- Two patients were monitored for 4 years without treatment, while four received interferon-alpha (IFN) therapy.
- Nucleotide and amino acid sequences of viral RNA amplicons were analyzed to assess genetic variation.
Main Results:
- SSCP analysis revealed 1-5 distinct GBV-C/HGV RNA bands and 1-4 HCV RNA bands per patient.
- GBV-C/HGV amplicons showed nucleotide variations but conserved amino acid sequences in the presumed antigenic region, unlike HCV's HVR.
- Predominant GBV-C/HGV strains remained stable in untreated patients, while IFN therapy led to the disappearance or persistence of specific strains.
- The mean genetic distance among GBV-C/HGV strains was significantly lower than that of HCV strains (P < 0.05).
Conclusions:
- GBV-C/HGV lacks significant antigenic drift and a hypervariable region comparable to HCV.
- GBV-C/HGV exhibits strain-specific sensitivity to interferon-alpha (IFN) therapy within the same host.
- These findings highlight distinct evolutionary and therapeutic response patterns between GBV-C/HGV and HCV.
Abstract:
GB virus C/hepatitis G virus (GBV-C/HGV) is related distantly to hepatitis C virus (HCV). HCV has a hypervariable region (HVR), and exists as quasispecies in vivo. Although GBV-C/HGV also has replaceable amino acids in the presumed antigenic region, the existence and fluctuation of population of heterogeneous virus have not been evaluated. In this study, the heterogeneity of GBV-C/HGV and HCV was investigated by the single-strand conformation polymorphism (SSCP) analysis in six concomitantly infected patients. Two patients were observed for 4 years without any treatment, and four were treated with interferon-alpha (IFN). By SSCP analysis, amplicons of GBV-C/HGV RNA were separated into 1-5 bands on gels for each patient. The amplicons had different nucleotide but the same amino acid sequences in the presumed antigenic region. The amplicons of HCV RNA, separated into 1-4 bands, had different nucleotide and amino acid sequences in the HVR. In the two patients without treatment, the predominant strain of GBV-C/HGV was unchanged for the 4 years. In the four patients administered IFN, some strains of GBV-C/HGV disappeared after IFN therapy, whereas other strains persisted. The mean genetic distance among GBV-C/HGV strains represented by SSCP analysis was significantly lower than that of HCV (P < 0.05). The data indicate that: 1) GBV-C/HGV can be devoid of antigenic drift unlike HCV; 2) GBV-C/HGV has no HVR as seen in HCV in the presumed antigenic region; and 3) the sensitivity to IFN differs among GBV-C/HGV strains in the same hosts, as with HCV.