Relationship of Genotypes of Hepatitis B Virus to Mutations,
Disease Progression and Response to Antiviral Therapy
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:
ˇ
Genotype
A is prevalent in north-western Europe, North America and
Africa.
ˇ
Genotypes
B and C are characteristic of Asia;
ˇ
Genotype
D has a worldwide distribution but predominates in the Mediterranean
area.
ˇ
Genotype
E is found in Africans,
ˇ
Genotype
F in the aboriginal populations of South America; and
ˇ
Genotype
H is confined to the Amerindian populations of Central America.
ˇ
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.
10/05/05
Reference
A Kramvis and M C Kew. Relationship of Genotypes of Hepatitis
B Virus to Mutations, Disease Progression and Response to
Antiviral Therapy. Journal of Viral Hepatitis 12(5):
456-464. September 2005.
