Contemporary and Historical Human Migration Patterns Shape Hepatitis B Virus Diversity

Infection by hepatitis B virus (HBV) is responsible for approximately 296 million chronic cases of hepatitis B, and roughly 880,000 deaths annually. The global burden of HBV is distributed unevenly, largely owing to the heterogeneous geographic distribution of its subtypes, each of which demonstrates different severity and responsiveness to antiviral therapy. It is therefore crucial to the global public health response to HBV that the spatiotemporal spread of each genotype is well characterized. In this study, we describe a collection of 133 newly sequenced HBV strains from recent African immigrants upon their arrival in Belgium. We incorporate these sequences-all of which we determine to come from genotypes A, D, and E-into a large-scale phylogeographic study with genomes sampled across the globe. We focus on investigating the spatio-temporal processes shaping the evolutionary history of the three genotypes we observe. We incorporate several recently published ancient HBV genomes for genotypes A and D to aid our analysis. We show that different spatio-temporal processes underlie the A, D, and E genotypes with the former two having originated in southeastern Asia, after which they spread across the world. The HBV E genotype is estimated to have originated in Africa, after which it spread to Europe and the Americas. Our results highlight the use of phylogeographic reconstruction as a tool to understand the recent spatiotemporal dynamics of HBV, and highlight the importance of supporting vulnerable populations in accordance with the needs presented by specific HBV genotypes.