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Long-term mutation rates in the hepatitis B virus genome
1Department of Clinical Virology, Göteborg University, Guldhedsgatan 10B, 413 46 Göteborg, Sweden.
The Journal of General Virology
|January 21, 2000
Summary
The hepatitis B virus (HBV) genome shows remarkable stability over decades, particularly during the hepatitis B e antigen-positive phase with weak immune response. Significant mutations emerge later, especially after hepatitis development or HBeAg loss, but without clear links to liver disease severity.
Area of Science:
- Virology
- Genetics
- Hepatology
Background:
- Long-term hepatitis B virus (HBV) genome evolution data is scarce due to sampling challenges.
- Previous studies primarily used cross-sectional or short-term longitudinal designs.
- Understanding long-term viral genetic changes is crucial for managing chronic HBV infection.
Purpose of the Study:
- To investigate long-term mutations in the HBV genome from transmission to late infection stages.
- To analyze HBV genome stability over approximately 26.5 years in vertically infected mother-child pairs.
- To correlate HBV mutations with clinical outcomes like hepatitis and HBeAg status.
Main Methods:
- Retrospective analysis of HBV genome sequences from vertically infected families.
- Whole-genome sequencing of serum samples from three mothers and 10 adult children.
- Comparison of individual viral sequences to the presumed transmitted ancestral strain.
Main Results:
- The HBV genome demonstrated high stability during the HBeAg-positive phase (0.02-0.28% sequence difference).
- An average of 20 mutations emerged in HBeAg-negative carriers or after hepatitis development (0.62% difference).
- Mutations were distributed throughout the genome, causing amino acid substitutions, but generally not linked to liver disease severity.
Conclusions:
- The HBV genome is highly stable over extended periods, especially when immune response is low during the HBeAg-positive phase.
- Viral evolution accelerates following hepatitis development and/or HBeAg loss.
- No specific mutations, apart from (1762)AGG(1764)-->TGA, were consistently associated with liver disease in this cohort.