ReviewHepatitis B virus intergenotypic recombinants worldwide: An overview

- Recombination is an important element of HBV genetic variability.
- HBV intergenotypic recombinants have widespread distribution around the globe.
- Recombination breakpoints are non-randomly distributed in the genome.

Novel variants generated by recombination events between different hepatitis B virus (HBV) genotypes have been increasingly documented worldwide, and the role of recombination in the evolutionary history of HBV is of significant research interest. In the present study, large-scale data retrieval and analysis on HBV intergenotypic recombinant genomes were performed. The geographical distribution of HBV recombinants as well as the molecular processes involved in recombination were examined. After review of published data, a total of 436 complete HBV sequences, previously identified as recombinants, were included in the recombination detection analysis. About 60% of HBV recombinants were B/C (n = 179) and C/D (n = 83) hybrids. A/B/C, A/C, A/C/G, A/D, A/E, A/G, B/C/U (U = unknown genotype), C/F, C/G, C/J, D/E, D/F, and F/G hybrids were additionally identified. HBV intergenotypic sequences were reported in almost all geographical regions with similar circulation patterns as their original genotypes, indicating the potential for spreading in a wide range of human populations and developing their own epidemiology. Recombination breakpoints were non-randomly distributed in the genome, and specific favored sites detected, such as within nt 1700-2000 and 2100-2300 regions, which displayed a statistically significant difference in comparison with the remaining genome. Elucidation of the effects of recombination events on the evolutionary history of HBV is critical to understand current and future evolution trends.