Related Experiment Videos
Evolution of the hepatitis B virus gene during chronic infection in seven patients
1Department of Pathology, Nihon University School of Medicine, Tokyo, Japan.
Insights
Hepatitis B virus (HBV) precore/core gene mutations evolve over time in chronic infections. These mutations correlate with clinical features, including seroconversion and reduced liver inflammation.
Area of Science:
- Virology
- Hepatology
- Molecular Biology
Background:
- Chronic hepatitis B virus (HBV) infection is a global health concern.
- The precore/core gene region of HBV plays a crucial role in viral replication and pathogenesis.
- Understanding the evolutionary dynamics of HBV quasispecies is essential for managing chronic infection.
Purpose of the Study:
- To analyze the long-term evolution of the HBV precore/core gene in patients with chronic infection.
- To correlate HBV genetic mutations with clinical manifestations and disease progression.
- To investigate the relationship between viral evolution and liver enzyme fluctuations.
Main Methods:
- Longitudinal sequence analysis of the HBV precore/core gene from seven patients over 6-11 years.
- Correlation of genetic mutations with clinical data, including HBeAg/anti-HBe status and alanine aminotransferase (ALT) levels.
- Identification of precore-defective mutants and core gene mutations.
Main Results:
- HBeAg to anti-HBe seroconversion correlated with precore-defective mutants, requiring years for complete replacement.
- Core gene mutations preceded precore mutations and increased over time, occurring during and after ALT elevations.
- ALT fluctuations subsided with complete wild-type replacement or substantial core gene mutation accumulation.
- Unexpectedly, both anti-HBe-positive and HBeAg-positive healthy carriers harbored wild-type precore genes, but the former showed rapid core gene evolution.
- A partial core gene deletion was observed during fatal hepatic failure in one patient.
Conclusions:
- HBV precore/core gene mutations are closely linked to the clinical features of chronic hepatitis B.
- Viral evolution, including precore and core gene mutations, influences disease progression and inflammatory activity.
- The findings highlight the dynamic nature of HBV infection and its genetic adaptation in vivo.
Abstract:
We analyzed the evolution of the precore/core gene of hepatitis B virus (HBV) over a period of 6 to 11 years in seven patients with chronic HBV infection, who exhibited a variety of clinical features. Sequence analysis revealed the following results: (1) HBeAg to anti-HBe seroconversion was correlated roughly with the occurrence of precore-defective mutants, and several years appeared to be required for complete replacement of wild types by mutants; (2) core gene mutations preceded precore-defective mutations and tended to increase with time, although not cumulatively. They occurred not only during serum alanine aminotransferase (ALT) elevations but also after ALT returned to normal; (3) ALT fluctuations appeared to subside with complete replacement of the wild type by the mutant type and/or substantial accumulation of core gene mutations; (4) unexpectedly, the anti-HBe-positive "healthy" carrier was found to harbor the wild type precore gene, as did the HBeAg-positive "healthy" carrier; however, the core gene of the former evolved at a rapid rate; and (5) a partial deletion was recognized in the core gene at the onset of fatal hepatic failure in one patient. Thus, the precore/core mutation was closely related with the clinical features in the patients.