Bayesian inference of the evolution of HBV/E.

Despite its wide spread and high prevalence in sub-Saharan Africa, hepatitis B virus genotype E (HBV/E) has a surprisingly low genetic diversity, indicating an only recent emergence of this genotype in the general African population. Here, we performed extensive phylogeographic analyses, including Bayesian MCMC modeling. Our results indicate a mutation rate of 1.9 × 10(-4) substitutions per site and year (s/s/y) and confirm a recent emergence of HBV/E, most likely within the last 130 years, and only after the transatlantic slave-trade had come to an end. Our analyses suggest that HBV/E originated from the area of Nigeria, before rapidly spreading throughout sub-Saharan Africa. Interestingly, viral strains found in Haiti seem to be the result of multiple introductions only in the second half of the 20th century, corroborating an absence of a significant number of HBV/E strains in West Africa several centuries ago. Our results confirm that the hyperendemicity of HBV(E) in today's Africa is a recent phenomenon and likely the result of dramatic changes in the routes of viral transmission in a relatively recent past

Slave Trade and Hepatitis B Virus Genotypes and Subgenotypes in Haiti and Africa

In Haiti, >90% of the population descended from African slaves. Of 7,147 Haitian pregnant women sampled, 44% of hepatitis B virus (HBV) infections were caused by genotype A1, which today is found mainly in eastern Africa. Twenty percent belong to a rare subgenotype, A5, which has been found only in the former Bight of Benin, a former primary slave trading post. Haitian A subgenotypes appear to have separated early from the African subgenotypes; the most prevalent genotype and subgenotype in West Africa today (E and A3, respectively) are rare in Haiti. This difference indicates that the dominant subgenotypes in Africa emerged in the general population only after the slave trade and explains the low genetic diversity of genotype E. The high prevalence of HBV genotype E in much of Africa further suggests that HBV hyperendemicity is a recent phenomenon, probably resulting from extensive use of unsafe needles

Origin and sampling date of analyzed HBV genotype S full-length and S-gene sequences.

<p>Origin and sampling date of analyzed HBV genotype S full-length and S-gene sequences.</p

Bayesian skyline plot showing the epidemic history of the HBV/E S-gene dataset.

<p>The plot indicates the median estimate of the effective population size, with the 95% highest posterior density indicated in blue. The applied timeframe ranges between the most recent sampling date and the calculated 130 years of evolution from the most recent common ancestor (MRCA), as calculated in the HBV/E full-length analysis.</p

Phylogeographic spread of HBV/E.

<p>The snapshots represent the geographic and temporal spread of HBV/E for which at least the S-gene and the spatial and temporal sampling information were available. A mutation rate of 7×10⁻⁵ s/s/y with the GTR+G+I model with geographic information was used. Spread analysis by the SPREAD software was visualized using Map Resources.</p

Phylogenetic analyses of all available HBV/E S-gene and full-length sequences.

<p>Analyses of S-gene (a) and full-length sequences (b) were performed using the GTR+G+I model with geographic information. Branching and roots of strains from individual countries are indicated by colors. Clusters with strains sampled in the same country and during the same year are collapsed.</p

Median Joining Network of HBV/E S-gene sequences.

<p>Pie charts represent sequence variants at the nodes, with colors indicating the country of sampling of individual sequences, the sizes reflecting the frequencies of the corresponding variants.</p

A High Variability of Mixed Infections and Recent Recombinations of Hepatitis B Virus in Laos

In Lao PDR, where more than 8 % of the population are chronic carriers of HBsAg, multiple genotypes and subgenotypes cocirculate and are prone to generate recombinant viruses. Phylogenetic analyses of multiple clones per donor revealed mixed infections of subgenotypes B1, B2, B4, C1, C5, I1 and I2 in almost 6 % of HBsAg positive rejected blood donors. Recombination analyses and distance calculations furthermore showed that about 65 % (17/26) of the mixed infected donors showed recombinations in the S-gene alone, involving the predominant genotypes B and C. These results suggest that, at least in Laos, hepatitis B virus (HBV) mixed infections lead to frequent recombinations. In many donors with recombinant strains, the recombinant fragment and a non-recombinant strain of the same genotype co-existed (127/185 analysed recombinant fragments). For a large proportion of these (60/127), the most closely related known virus was found, although not always exclusively, in the same donor. Recombinant virus strains are largely distinct. This is reflected in an unexpected diversity in recombination breakpoints and the relatively rare recombinations with identical recombination patterns of the same genotypes in different donors. Recent recombination events would explain the limited spread of each of the recombinants. Using a published mutation rate of 4.2610 25 mutations per site and year, the observed minimum genetic distances of 0–0.60 % between parent strain and recombinant fragment would correspond to 0–71 years of evolution from a most recent common ancestor (MRCA). Thus several lines of evidence are suggestive of recen

Sub-/genotypes in HBV mixed infections in Lao PDR.

<p>*n/a: not applicable.</p