Conserved recombination patterns across hepatitis B genotypes: a retrospective study

Abstract Hepatitis B virus (HBV) infection is a major public health concern, as chronic HBV infection can lead to liver cirrhosis and increase a person’s risk of developing hepatocellular carcinoma (HCC). HBV has been classified into ten genotypes (A to J). Here, we analysed the genotypic diversity...

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Main Authors: Derek Tshiabuila, James E. San, Eduan Wilkinson, Graeme Dor, Houriiyah Tegally, Tongai G. Maponga, Marion Delphin, Philippa C. Matthews, Darren P. Martin, Cheryl Baxter, Tulio de Oliveira
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Virology Journal
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Online Access:https://doi.org/10.1186/s12985-025-02829-0
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author Derek Tshiabuila
James E. San
Eduan Wilkinson
Graeme Dor
Houriiyah Tegally
Tongai G. Maponga
Marion Delphin
Philippa C. Matthews
Darren P. Martin
Cheryl Baxter
Tulio de Oliveira
author_facet Derek Tshiabuila
James E. San
Eduan Wilkinson
Graeme Dor
Houriiyah Tegally
Tongai G. Maponga
Marion Delphin
Philippa C. Matthews
Darren P. Martin
Cheryl Baxter
Tulio de Oliveira
author_sort Derek Tshiabuila
collection DOAJ
description Abstract Hepatitis B virus (HBV) infection is a major public health concern, as chronic HBV infection can lead to liver cirrhosis and increase a person’s risk of developing hepatocellular carcinoma (HCC). HBV has been classified into ten genotypes (A to J). Here, we analysed the genotypic diversity and recombination patterns of HBV using 14486 publicly available HBV genome sequences. Partial sequences and sequences with no metadata were filtered out, resulting in a final dataset of 8823 HBV genomes. These sequences were then combined with 41 HBV reference genomes from NCBI GenBank, and a maximum-likelihood phylogenetic tree was constructed to generate ten HBV genotype datasets. Multiple sequence alignment was performed for each HBV dataset, and using RDP5.64, we identified 288 unique recombination events. Inter-genotype B/C recombination events were most common (found in 626/1194 identified recombinants), including 22/66 recombination events detected in viruses that are phylogenetically genotype B and 22/78 that are phylogenetically genotype C. The HBx (X) and pre-Core (pre-C) regions of the HBV genome were identified as recombination breakpoint hotspots, with the pre-C region also being the most frequently transferred genome region during recombination. As with many other viruses, the observed recombination breakpoint patterns in HBV genomes are significantly attributable to factors such as local sequence similarity, GC content, or selection against recombination-induced protein misfolding. This study highlights the complexity of the genetic diversity and recombination of HBV, with important implications for understanding its evolution and informing tailored public health interventions.
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spelling doaj-art-584a27c44d9a48f69b5ed18fde9ffee82025-08-20T03:45:27ZengBMCVirology Journal1743-422X2025-07-0122111510.1186/s12985-025-02829-0Conserved recombination patterns across hepatitis B genotypes: a retrospective studyDerek Tshiabuila0James E. San1Eduan Wilkinson2Graeme Dor3Houriiyah Tegally4Tongai G. Maponga5Marion Delphin6Philippa C. Matthews7Darren P. Martin8Cheryl Baxter9Tulio de Oliveira10Centre for Epidemic Response and Innovation (CERI), School for Data Science and Computational Thinking, Stellenbosch UniversityDuke Human Vaccine Institute, Duke University Medical CenterCentre for Epidemic Response and Innovation (CERI), School for Data Science and Computational Thinking, Stellenbosch UniversityCentre for Epidemic Response and Innovation (CERI), School for Data Science and Computational Thinking, Stellenbosch UniversityCentre for Epidemic Response and Innovation (CERI), School for Data Science and Computational Thinking, Stellenbosch UniversityDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University & National Health Laboratory ServiceThe Francis Crick InstituteThe Francis Crick InstituteComputational Biology Division, Department of Integrative Biomedical Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape TownCentre for Epidemic Response and Innovation (CERI), School for Data Science and Computational Thinking, Stellenbosch UniversityCentre for Epidemic Response and Innovation (CERI), School for Data Science and Computational Thinking, Stellenbosch UniversityAbstract Hepatitis B virus (HBV) infection is a major public health concern, as chronic HBV infection can lead to liver cirrhosis and increase a person’s risk of developing hepatocellular carcinoma (HCC). HBV has been classified into ten genotypes (A to J). Here, we analysed the genotypic diversity and recombination patterns of HBV using 14486 publicly available HBV genome sequences. Partial sequences and sequences with no metadata were filtered out, resulting in a final dataset of 8823 HBV genomes. These sequences were then combined with 41 HBV reference genomes from NCBI GenBank, and a maximum-likelihood phylogenetic tree was constructed to generate ten HBV genotype datasets. Multiple sequence alignment was performed for each HBV dataset, and using RDP5.64, we identified 288 unique recombination events. Inter-genotype B/C recombination events were most common (found in 626/1194 identified recombinants), including 22/66 recombination events detected in viruses that are phylogenetically genotype B and 22/78 that are phylogenetically genotype C. The HBx (X) and pre-Core (pre-C) regions of the HBV genome were identified as recombination breakpoint hotspots, with the pre-C region also being the most frequently transferred genome region during recombination. As with many other viruses, the observed recombination breakpoint patterns in HBV genomes are significantly attributable to factors such as local sequence similarity, GC content, or selection against recombination-induced protein misfolding. This study highlights the complexity of the genetic diversity and recombination of HBV, with important implications for understanding its evolution and informing tailored public health interventions.https://doi.org/10.1186/s12985-025-02829-0Hepatitis B virus (HBV)Genotypic diversityViral recombinationRecombination hotspotsPhylogeneticsViral evolution
spellingShingle Derek Tshiabuila
James E. San
Eduan Wilkinson
Graeme Dor
Houriiyah Tegally
Tongai G. Maponga
Marion Delphin
Philippa C. Matthews
Darren P. Martin
Cheryl Baxter
Tulio de Oliveira
Conserved recombination patterns across hepatitis B genotypes: a retrospective study
Virology Journal
Hepatitis B virus (HBV)
Genotypic diversity
Viral recombination
Recombination hotspots
Phylogenetics
Viral evolution
title Conserved recombination patterns across hepatitis B genotypes: a retrospective study
title_full Conserved recombination patterns across hepatitis B genotypes: a retrospective study
title_fullStr Conserved recombination patterns across hepatitis B genotypes: a retrospective study
title_full_unstemmed Conserved recombination patterns across hepatitis B genotypes: a retrospective study
title_short Conserved recombination patterns across hepatitis B genotypes: a retrospective study
title_sort conserved recombination patterns across hepatitis b genotypes a retrospective study
topic Hepatitis B virus (HBV)
Genotypic diversity
Viral recombination
Recombination hotspots
Phylogenetics
Viral evolution
url https://doi.org/10.1186/s12985-025-02829-0
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