Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations.

One hundred and twenty-two new hepatitis B virus (HBV) preC/C sequences and three complete genomes from three major countries in West Africa were analysed. The majority of sequences were of genotype E and the only other genotype found was genotype A. Although for genotype E sequences, the genetic diversity of the preC/C gene was about two to three times higher than that of the preS/S gene, it was still considerably lower than that for genotype A sequences. The HBV/E preC/C gene was related most closely to subgenotype D1 and D2 sequences. Evidence of recombination was found in two strains that were of genotype A in the preS/S gene and of genotype E in the preC/C gene. The genotype A strains from Cameroon, Mali and Nigeria could be divided phylogenetically into three subtypes, A3 and two new subtypes, tentatively designated A4 and A5. Each subtype presented a genetic diversity of 2.19-3.85 % and intersubtype distances of 4.47-5.97 %. Interestingly, one sample from Nigeria showed evidence of a triple recombination of genotypes E/D and A, separated by a genotype G-specific insert of 36 bp. Of 110 patients, 19 (17.3 %) showed a coinfection of genotypes A and E, mostly in human immunodeficiency virus-positive children from Cameroon. Thus, in Cameroon, where both genotypes coexist, 37 % of all individuals tested had mixed infections. The low genetic variability in the preC/C gene of genotype E supports our previous speculation about a relatively short evolutionary history of this genotype, in contrast to the subtype-rich African genotype A strains.

Low genetic diversity despite hyperendemicity of hepatitis B virus genotype E throughout West Africa.

Sub-Saharan Africa suffers from an excessively high endemicity of hepatitis B virus (HBV), but little is known about the prevalent genotypes. In this study, we investigated the PreS1/PreS2/S genes of 127 viruses obtained from 12 locations in Mali, Burkina Faso, Togo, Benin, Nigeria, Cameroon, and the Democratic Republic of Congo. Except for those obtained from the Cameroon HIV cohort (18/22 HBV genotype A), 96 of 105 sequences belonged to HBV genotype E (HBV/E), and viral DNA was very similar (1.67% diversity) throughout this vast HBV/E crescent, which spans 6000 km across Africa. The low diversity suggests that HBV/E may have a short evolutionary history. Considering a typical mutation rate of DNA viruses, it would take only 200 years for the strain diversity of HBV/E viruses to develop from a single introductory event. The relatively recent introduction of HBV/E into humans would also explain its conspicuous absence in the Americas, despite the forced immigration of slaves from west Africa, until the early 19th century. Infection during infancy is mostly associated with chronic carrier status, and this combination can account for the explosive spread of virtually identical viruses within a community, but whether other routes of long-range transmissions must be considered becomes an important question.