Conserved recombination patterns across hepatitis B genotypes: a retrospective study

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.