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Selection for a pre-C stop codon mutation in a hepatitis B virus variant with a pre-C initiation codon mutation
T Santantonio1, M C Jung, R Schneider
1Max-Planck-Institut für Biochemie, Martinsried/München, Federal Republic of Germany.
Journal of Hepatology
|November 1, 1991
Summary
Hepatitis B virus (HBV) pre-C variants with stop codon mutations are selected during chronic infection. Interferon treatment further increases the prevalence of these mutations, suggesting immune-mediated selection.
Area of Science:
- Virology
- Hepatology
- Immunology
Background:
- Hepatitis B virus (HBV) pre-C region mutations can prevent the expression of hepatitis B e-antigen (HBeAg).
- These mutations are common in individuals with chronic HBV infection who are anti-HBe positive.
- Previous studies identified pre-C variants with two mutations preventing HBeAg expression.
Observation:
- This study investigated the selective pressure for acquiring a second pre-C mutation in HBV.
- Direct sequencing of HBV DNA from a chronic carrier over 6 years was performed.
- Initially, most HBV genomes had a pre-C translation initiation codon mutation, with 50% having an additional stop codon mutation.
Findings:
- Interferon treatment led to a significant increase in stop codon mutations, exceeding 95%.
- The frequency of the translation initiation codon mutation remained constant throughout the follow-up.
- These results indicate positive selection for the second pre-C mutation, likely immune-mediated and HBeAg-targeted.
Implications:
- The findings suggest that a single pre-C mutation may not completely abolish HBeAg expression.
- Acquisition of a second mutation enhances translational control, potentially reducing HBeAg levels.
- This selective pressure may be crucial in managing chronic Hepatitis B infection and its outcomes.