Molecular characteristics and clinical relevance of African genotypes and subgenotypes of hepatitis B virus

Abstract

Hepatitis B virus (HBV), a DNA virus, replicates via an RNA intermediate, through reverse transcription catalysed by the viral polymerase that lacks proof reading ability. Thus sequence heterogeneity is a feature of HBV being classified into at least 9 genotypes and over 35 subgenotypes. Africa has a high diversity of genotypes/subgenotypes, with distinct geographical distributions. Genotype A is found mainly in south-eastern Africa, E in western and central Africa and D prevailing in northern Africa. Outside Africa, subgenotype A2 prevails and A1 in Africa, which was the most probable source of its dispersal to Asia and Latin America, as a result of slave and trade routes. Genotype E is also an African strain with low genetic diversity, intimating a recent emergence of 200 years or less, with its dispersal outside Africa occurring as a result of modern human migrations. Carriers of subgenotype A1 and genotype E display unique clinical features. A1-infected individuals have low viral loads, low frequency of HBeAg-positivity, horizontal transmission of HBV, higher levels of liver damage and a higher risk of developing hepatocellular carcinoma. In contrast, individuals infected with genotype E have high viral loads, high frequency of HBeAg-positivity and transmit HBV perinatally. Although 15% of HBV infections in HIV-infected Africans are HBsAg-negative, the true occult phenotype of low viral loads is found in only 7% and 65% of individuals infected with subgenotype A1 and genotypes E (or D), respectively. Molecular and functional characteristics of these African HBV strains can account for their different clinical manifestations.