High Frequency of Either Altered Pre-Core StartCodon or Weakened Kozak Sequence in the CorePromoter Region in Hepatitis B Virus A1 Strainsfrom Rwanda.

Heléne Norder,Joanna Said,Theogene Twagirumugabe,Magnus Lindh,Ka-Wei Tang,Yarong Tian

doi:10.3390/genes10030182

Abstract

Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.

Highlights

Hepatitis B virus (HBV) is a DNA virus of the family of Hepadnaviridae
Complete genomes were obtained for 23 HBV A1 strains
Phylogenetic analysis of the complete genomes confirmed that most HBV strains from Rwanda, together with two strains from the neighboring Tanzania and one from Democratic Republic of Congo formed a single clade, within subgenotype A1 (Figure 1)

Summary

Introduction

Hepatitis B virus (HBV) is a DNA virus of the family of Hepadnaviridae. It has a compact genome of about 3.2 kb with a genetic variability classifying the strains into nine genotypes (A-I) [1,2,3,4], each further subdivided into subgenotypes. The HBV genome has four overlapping open reading frames (ORF), the preS1/S2/S coding for surface antigens, the P encoding the polymerase, the precore/C encoding for both the circulating e-antigen (HBeAg) and the core antigen, and the X ORF encoding the HBx protein. There are seven polyadenylated and capped viral RNA transcripts which encode the viral proteins [9,10].

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