Relationship of Genotypes of Hepatitis B Virus
Relationship of Genotypes of Hepatitis B Virus
Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also be responsible for differences in the clinical outcome and response to antiviral treatment in different population groups.
Hepatitis B virus (HBV), a DNA virus, is a member of the family Hepadnaviridae that replicate by reverse transcription of the encapsidated pregenomic RNA by the viral encoded polymerase. The viral polymerase lacks proofreading activity and sequence heterogeneity is therefore a feature of HBV.
Phylogenetic analysis has led to the classification of HBV into eight genotypes, defined by an inter-group divergence of >8% in the complete genome sequence and of >4% in the S gene. Since the first description of four genotypes (A-D) of HBV in 1988, four more have been identified, designated E and F, G and H. Moreover, subgenotypes with distinctive sequence characteristics and a divergence in the complete genome of >4% have been found within genotypes A, B, C and F.
The eight genotypes show a distinctive geographical distribution. Genotype A is prevalent in north-western Europe, North America and Africa. Genotypes B and C are characteristic of Asia, whereas genotype D has a worldwide distribution but predominates in the Mediterranean area. Genotype E is found in Africans, genotype F in the aboriginal populations of South America and genotype H is confined to the Amerindian populations of Central America. To date, the isolation of genotype G has been limited to HBV carriers in France and Georgia, USA, UK, Italy and Germany.
The first instance of genotype-related differences in the biological properties of HBV was the observation that the precore 1896 stop-codon mutant was commonly found in regions where genotype D prevailed and was absent in regions were genotype A occurred. The reason for the association of the 1896 mutant with genotype D was that this mutation enhanced the stability of the encapsidation signal (ε) allowing replication, whereas in genotype A it would lead to its destabilization and therefore prevent replication. Subsequently, it has become increasingly evident that the heterogeneity in the global distribution of HBV genotypes may account not only for differences in the prevalence of HBV mutations in the different populations but also be responsible for differences in the clinical outcomes of HBV infections and the response to antiviral treatment.
Phylogenetic analysis has led to the classification of hepatitis B virus into eight genotypes, designated A to H. The genotypes have differences in biological properties and show heterogeneity in their global distribution. These attributes of the genotypes may account not only for differences in the prevalence of hepatitis B virus mutants in various geographic regions, but also be responsible for differences in the clinical outcome and response to antiviral treatment in different population groups.
Hepatitis B virus (HBV), a DNA virus, is a member of the family Hepadnaviridae that replicate by reverse transcription of the encapsidated pregenomic RNA by the viral encoded polymerase. The viral polymerase lacks proofreading activity and sequence heterogeneity is therefore a feature of HBV.
Phylogenetic analysis has led to the classification of HBV into eight genotypes, defined by an inter-group divergence of >8% in the complete genome sequence and of >4% in the S gene. Since the first description of four genotypes (A-D) of HBV in 1988, four more have been identified, designated E and F, G and H. Moreover, subgenotypes with distinctive sequence characteristics and a divergence in the complete genome of >4% have been found within genotypes A, B, C and F.
The eight genotypes show a distinctive geographical distribution. Genotype A is prevalent in north-western Europe, North America and Africa. Genotypes B and C are characteristic of Asia, whereas genotype D has a worldwide distribution but predominates in the Mediterranean area. Genotype E is found in Africans, genotype F in the aboriginal populations of South America and genotype H is confined to the Amerindian populations of Central America. To date, the isolation of genotype G has been limited to HBV carriers in France and Georgia, USA, UK, Italy and Germany.
The first instance of genotype-related differences in the biological properties of HBV was the observation that the precore 1896 stop-codon mutant was commonly found in regions where genotype D prevailed and was absent in regions were genotype A occurred. The reason for the association of the 1896 mutant with genotype D was that this mutation enhanced the stability of the encapsidation signal (ε) allowing replication, whereas in genotype A it would lead to its destabilization and therefore prevent replication. Subsequently, it has become increasingly evident that the heterogeneity in the global distribution of HBV genotypes may account not only for differences in the prevalence of HBV mutations in the different populations but also be responsible for differences in the clinical outcomes of HBV infections and the response to antiviral treatment.