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Updated: Aug 18, 2026

Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
A new intertype recombinant between genotypes C and D of hepatitis B virus identified in China
Zhanhui Wang1,2, Zhihua Liu1, Guobing Zeng1
1Department of Infectious Diseases, Nanfang Hospital, Guangzhou 510515, China.
Insights
Hepatitis B virus (HBV) isolates initially classified as genotype D were found to be recombinants of genotypes C and D. This intertype recombination increases HBV genetic diversity and may impact diagnosis and treatment.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- Hepatitis B virus (HBV) genotypes exhibit distinct geographical distributions, with genotypes B and C predominant in China.
- Accurate HBV genotype classification is crucial for understanding disease progression and treatment strategies.
Purpose of the Study:
- To investigate the genetic characteristics of eight HBV isolates initially classified as genotype D.
- To determine if intertype recombination has occurred in these HBV isolates and identify recombination sites.
Main Methods:
- Complete HBV genome sequencing and comparison with reference sequences from genotypes A-G.
- Phylogenetic analyses of different HBV open reading frames (ORFs), including the S, precore/core, and X genes.
- Recombination analysis using the simplot program.
Main Results:
- Phylogenetic analysis of the S gene indicated genotype D, while analyses of other ORFs suggested genotype C.
- Discordant phylogenetic results across different ORFs indicated intertype recombination in all eight isolates.
- Recombination with genotype D was localized to the preS2/S region in most isolates.
Conclusions:
- Intertype recombination is a significant source of genetic diversity in Hepatitis B virus.
- HBV genotype hybrids may possess unique virological properties requiring further investigation for clinical implications in chronic hepatitis B management.
Abstract:
Hepatitis B virus (HBV) genotypes have a characteristic geographical distribution. More than 90% of chronic HBV patients in China are infected with genotypes B or C. Here, eight HBV isolates that were initially classified as genotype D by PCR-restriction fragment length polymorphism analysis were analysed in detail. The complete HBV genome was sequenced and compared with 32 sequences retrieved from GenBank, representing HBV genotypes A-G. Phylogenetic analysis of the S gene (nt 10-800) classified all eight isolates as genotype D. However, phylogenetic analyses of nt 800-10 and the open reading frames (ORFs) of the precore/core and X genes classified all eight isolates as genotype C. This discordance between phylogenetic trees reconstructed on different ORFs suggested that intertype recombination has occurred in all eight isolates. By using the simplot program, the site of recombination with genotype D was located in the preS2/S region, spanning nt 10-799 in seven of eight isolates and nt 10-1499 in the other isolate. These results demonstrate that intertype recombination should be considered as a type of variation that increases the genetic diversity of HBV. Hybrids of different HBV genotypes might exhibit specific virological properties and their significance in the diagnosis and management of chronic hepatitis B deserves further investigation.
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