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

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Abstract
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.