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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Evolutionary pattern of full hepatitis B virus genome during sequential nucleos(t)ide analog therapy
Ying-Zi Tang1, Lin Liu, Mei-Min Pan
1Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
Antiviral Research
|March 29, 2011
Summary
Hepatitis B virus (HBV) evolution differs significantly between treated and untreated patients. Nucleos(t)ide analog (NUC) therapy alters HBV quasispecies, impacting viral genetic variability and epitopes.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- The evolutionary dynamics of hepatitis B virus (HBV) quasispecies under nucleos(t)ide analog (NUC) therapy are not fully understood.
- Sequential NUC treatments represent a common clinical strategy for managing chronic HBV infection.
Purpose of the Study:
- To investigate the evolutionary and mutational patterns of full-length HBV quasispecies during sequential NUC therapy.
- To compare HBV genetic variability in treated patients versus untreated patients experiencing acute flares.
Main Methods:
- Generation of full-length HBV clones from serial serum samples of treated and untreated patients.
- Analysis of nucleotide polymorphism and nonsynonymous divergence across the HBV genome.
- Identification of mutations within key regions, including the "a" determinant, T-cell/B-cell epitopes, and reverse transcriptase (RT).
Main Results:
- NUC therapy altered HBV quasispecies evolution, with distinct patterns observed during lamivudine and sequential adefovir-telbivudine treatments.
- Untreated patients showed increased polymorphism and divergence in the preC/C region during acute flares.
- Treated patients exhibited amino acid changes in viral epitopes, often coinciding with RT mutations, while untreated patients showed co-variations primarily in the preC/C gene.
Conclusions:
- HBV quasispecies divergence exhibits markedly different patterns in NUC-treated versus untreated individuals.
- Regional genetic variability within HBV can fluctuate significantly even within a single host during treatment.
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