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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Viral quasi-species evolution during hepatitis Be antigen seroconversion
Seng Gee Lim1, Yan Cheng, Stephane Guindon
1Department of Gastroenterology and Hepatology, National University Hospital, Singapore. mdclimsg@nus.edu.sg
Gastroenterology
|September 15, 2007
Summary
Hepatitis B virus (HBV) evolution shows higher diversity and substitution rates in patients who achieve hepatitis B e antigen (HBeAg) seroconversion. This increased viral evolution may indicate a breakdown in immune tolerance or heightened immune responses driving viral escape mutations.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Viral quasi-species evolution is linked to disease pathogenesis, but its role in Hepatitis B Virus (HBV) is not well understood.
- Chronic hepatitis B presents diverse clinical phenotypes, including hepatitis B e antigen (HBeAg) seroconverters and non-seroconverters.
Purpose of the Study:
- To investigate the evolution of HBV quasi-species in patients with distinct clinical phenotypes of chronic hepatitis B.
- To correlate viral evolution patterns with clinical outcomes like HBeAg seroconversion.
Main Methods:
- Analysis of serum samples from four cohorts with defined chronic hepatitis B phenotypes over approximately 60 months.
- Nested PCR, cloning, and sequencing of the HBV precore/core gene from multiple time points for 3386 viral sequences (genotype B only).
- Phylogenetic analysis and estimation of viral diversity and substitution rates using advanced computational models.
Main Results:
- HBeAg seroconverters exhibited significantly higher preseroconversion viral sequence diversity (2.4-fold) and substitution rates (10-fold) compared to non-seroconverters.
- Non-seroconverters maintained persistently low viral diversity and substitution rates.
- A notable increase in viral diversity was observed post-seroconversion, with evidence of positive selection in most seroconverters.
Conclusions:
- Elevated viral diversity preceding HBeAg seroconversion may signify stochastic mutations leading to immune tolerance loss.
- Alternatively, increased viral diversity could reflect heightened immune reactivity driving viral escape mutations.
- Understanding HBV quasi-species evolution is crucial for deciphering chronic hepatitis B pathogenesis and immune dynamics.
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