Hepatitis C virus envelope glycoprotein co-evolutionary dynamics during chronic hepatitis C

Area of Science:

• Virology
• Immunology
• Hepatology

Background:

• Hepatitis C virus (HCV) infection remains a significant global health concern.
• Understanding HCV quasispecies evolution is crucial for disease progression insights.
• The interplay between viral evolution and liver disease severity is not fully elucidated.

Purpose of the Study:

• To investigate the co-evolution of Hepatitis C virus (HCV) envelope glycoproteins (E1 and HVR1) in relation to liver disease severity.
• To compare viral evolution patterns in treatment-naive patients with mild versus severe liver disease.

Main Methods:

• Longitudinal analysis of HCV genotype 1 envelope gene (E1 and HVR1) sequences from 14 treatment-naive subjects (7 mild, 7 severe liver disease).
• Isolation of gene cassettes over 81 follow-up years at 38 time points.
• Phylogenetic analysis to compare amino acid sequence similarity and evolutionary rates.

Main Results:

• No significant differences in age, gender, alcohol use, or viral load between mild and severe disease groups.
• Virus from severe disease subjects exhibited significantly slower evolution in the HVR1 region.
• Divergent evolution of E1 quasispecies, with a higher proportion of synonymous mutations, was observed in severe disease.
• Phylogenetic comparisons revealed higher amino acid sequence similarity for E1 and HVR1 in mild disease (r=0.44) versus severe disease (r=0.17, P=0.01).

Conclusions:

• HCV envelope quasispecies co-evolution patterns are distinct in mild versus severe liver disease.
• Slower HVR1 evolution and altered E1 quasispecies dynamics characterize severe HCV infection.
• These findings highlight the impact of disease severity on viral evolution and may inform future therapeutic strategies.