Spatial and temporal dynamics of hepatitis B virus D genotype in Europe and the Mediterranean Basin

Abstract

Hepatitis B virus genotype D can be found in many parts of the world and is the most prevalent strain in south-eastern Europe, the Mediterranean Basin, the Middle East, and the Indian sub-continent. The epidemiological history of the D genotype and its subgenotypes is still obscure because of the scarcity of appropriate studies. We retrieved from public databases a total of 312 gene P sequences of HBV genotype D isolated in various countries throughout the world, and reconstructed the spatio-temporal evolutionary dynamics of the HBV-D epidemic using a bayesian framework.The phylogeographical analysis showed that India had the highest posterior probability of being the location of the tree root, whereas central Asia was the most probable location of the common ancestor of subgenotypes D1-D3. HBV-D5 (identified in native Indian populations) diverged from the tree root earlier than D1-D3. The time of the most recent common ancestor (tMRCA) of the tree root was 128 years ago, which suggests that the common ancestor of the currently circulating subgenotypes existed in the second half of the XIX century. The mean tMRCA of subgenotypes D1-D3 was between the 1940s and the 1950-60s. On the basis of our phylogeographic reconstruction, it seems that HBV-D reached the Mediterranean area in the middle of the XX century by means of at least two routes: the first pathway (mainly due to the spread of subgenotype D1) crossing the Middle East and reaching north Africa and the eastern Mediterranean, and the second pathway (closely associated with D2) that crossed the former Soviet Union and reached eastern Europe and the Mediterranean through Albania. We hypothesise that the main route of dispersion of genotype D was the unsafe use of injections and drug addiction.

Figure 1. The maximum clade credibility (MCC) tree of HBV-D P gene sequences.

The branches are coloured on the basis of the most probable location state of the descendent nodes (see colour codes in upper left inset). The numbers on the internal nodes represent posterior probabilities, and the scale at the bottom of the tree represents the years before the last sampling time (2007). The clades corresponding to the main HBV-D subgenotypes (D1, D2, D3, D5, D7) are highlighted.

Figure 2. Significant non-zero HBV-D migration rates worldwide.

Only the rates supported by a BF of >6 are shown. The relative strength of the support is indicated by the colour of the lines (from dark red = weak to light red = strong). The map was reconstructed using SPREAD (see Methods).