Hepatitis B genotyping: The utility for the clinicians
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TECHNICAL NOTES
Hepatitis B genotyping: The utility for the clinicians Gnanadurai John Fletcher 1 & Chundamannil Eapen Eapen 2
&
Priya Abraham 1
# Indian Society of Gastroenterology 2019
Hepatitis B virus (HBV) genome and the origin of genotype The HBV belongs to the family Hepadnaviridae. The HBV genome is about 3200 base pairs (bps) in size and is partially double stranded [1]. It is maintained in relaxed circular conformation by cohesive 5′ ends of the deoxy ribonucleic acid (DNA) strands. In addition to the complex and the compact nature of its genome, HBV also displays conspicuous genome economy by the presence of multiple overlapping open reading frames (ORFs) [2]. Unlike other DNA viruses, HBV replication involves a critical reverse transcription step [1]. This step involves ribonucleic acid (RNA)-dependent DNA polymerase, which lacks proofreading activity leading to error-prone viral replication [2]. The rate of nucleotide substitutions per site is about 2.1 × 10−5 per year with the mean observation period of 22 years [2]. It is postulated that hepatitis B e antigen (HBeAg)-positive carriers are more likely to transmit the virus across human generations. Under such transmission and substitution probabilities, the best conservative extrapolation reveals that HBV would have originated from the most recent common ancestor about 2300– 3100 years ago [2]. The error-prone replication acts as a major molecular factor for the emergence of genotypes and sub-genotypes [3]. Intergenotypic recombination further accentuates the evolution of HBV [3]. As a proof, genotype I is a novel tri-recombinant of genotypes A, C and G [4]. Genotype J shows high similarity with gibbon genotypes and human genotype C [5]. Hence,
* Chundamannil Eapen Eapen [email protected] 1
Department of Virology, Christian Medical College, Vellore, 632 004, India
2
Department of Hepatology, Christian Medical College, Vellore, 632 004, India
evolution of HBV genotypes requires comprehensive molecular investigation to understand its influence on pathogenesis and outcome of HBV infection.
Definition of HBV genotypes HBV is classified based on the phylogenetic analyses of the complete viral genome. Degree of nucleotide divergence in the complete genome is a molecular criterion for the designation of genotypes and sub-genotypes [6]. According to standard guidelines, genotypes and sub-genotypes are designated based on 8% (inter-group) and 4% to 8% (inter-genotype) nucleotide divergence respectively [6]. HBV genotype prevalence varies geographically. To date, 10 genotypes, A through J, and 35 sub-genotypes have been identified. The prevalence of genotypes shows geographical restriction: genotype A is prevalent in Africa, India, Europe and America; genotypes B and C are widely prevalent in Asia-Pacific; genotype D is prevalent in India, Africa, Mediterranean regions and Europe; genotype E is widely prevalent in West Africa; genotype F is seen in South and Central Americas; genotype I is largely restricted to Vietnam and Laos; and genotype J i
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