Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences

Abstract

Hepatitis B virus (HBV) is a diverse, partially double-stranded DNA virus, with 9 genotypes (A-I), and a putative 10th genotype (J), thus far characterised. Given the broadening interest in HBV sequencing, there is an increasing requirement for a consistent, unified approach to HBV genotype and subgenotype classification. We set out to generate an updated resource of reference sequences using the diversity of all genomic-length HBV sequences available in public databases. We collated and aligned genomic-length HBV sequences from public databases and used maximum-likelihood phylogenetic analysis to identify genotype clusters. Within each genotype, we examined the phylogenetic support for currently defined subgenotypes, as well as identifying well-supported clades and deriving reference sequences for them. An alignment of these reference sequences and maximum-likelihood phylogenetic trees of the sequences are provided to simplify classification. Based on the phylogenies generated, we present a comprehensive set of HBV reference sequences at the genotype and subgenotype level.

Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis

“…In addition, deletion of viral domains such as the HBV preS region may also contribute towards risks of HCC or recurrence of HCC, such as the recent reports by Teng et al [ 38 ] HBV is currently classified into 10 different genotypes, labeled A to J, which are defined as >7.5% genetic divergence within the full genome sequence of the virus [ 39 , 40 ]. Furthermore, HBV is separated into a number of subgenotypes defined as 4 to 7.5% genetic divergence [ 41 , 42 ]. Traditionally, over 30 different HBV subgenotypes have been identified and classified [ 41 ].…”

“…Traditionally, over 30 different HBV subgenotypes have been identified and classified [ 41 ]. However, recent studies utilizing powerful sequencing data and phylogenetic analysis have suggested a careful revision of the number and standardization of subgenotypes [ 42 , 43 ]. HBV genotypes are typically geographically distributed.…”

Hepatitis B virus preS2Δ38–55 variants: A newly identified risk factor for hepatocellular carcinoma

“…In addition, as patients with HCC in SSA present at advanced stages, we were unable to recruit individuals with early small tumours, and all patients had tumours >5 cm (data not shown). Finally, whilst our partial HBV sequences (surface genes) are sufficient for genotyping, 3,4 they are not for sub-genotyping as numerous misclassifications will arise, [42][43][44] and this issue needs to be resolved in future studies.…”

Endemic hepatitis B virus (HBV) among hospital in-patients in Bangladesh, including evidence of occult infection

“…(which was not certified by peer review) published HBV sequences from Bangladesh. Four full-length HBV consensus sequences generated in this study were analysed alongside HBV genotype reference sequences (for genotypes A-J) 42 and 61 sequences originating from Bangladesh identified in Genbank 66 (unlabelled branches, Suppl Table 1). Genotype A sequences are highlighted in blue, genotype C in red and genotype D in yellow.…”