Reconstruction of the origin and dispersal of the worldwide dominant Hepatitis B Virus subgenotype D1

Background Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV-D1 is the dominant subgenotype in the Mediterranean basin, Eastern Europe and Asia. However, little is currently known about its evolutionary history and spatio-temporal dynamics. Methods We use Bayesian phylodynamic inference to investigate the temporal history of HBV-D1, for which we calibrate the molecular clock using ancient sequences, and reconstruct the viral global spatial dynamics based, for the first time, on full-length publicly available HBV-D1 genomes from a wide range of sampling dates. Results We pinpoint the origin of HBV subgenotype D1 before the current era (BCE) in Turkey/Anatolia. The spatial reconstructions reveal global viral transmission with a high degree of mixing. Conclusions By combining modern-day and ancient sequences, we ensure sufficient temporal signal in HBV-D1 data to enable Bayesian phylodynamic inference using a molecular clock for time calibration. Our results shed light on the worldwide HBV-D1 epidemics and suggest that this originally Middle Eastern virus significantly affects more distant countries, such as those in mainland Europe.