Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation

Abby Harrison, Philippe Lemey, Matthew Hurles, Chris Moyes, Susanne Horn, Jan Pryor, Joji Malani, Mathias Supuri, Andrew Masta, Burentau Teriboriki, Tebuka Toatu, David Penny, Andrew Rambaut, Beth Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements.

Original languageEnglish
Pages (from-to)83-101
Number of pages19
JournalViruses
Volume3
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • hepatitis B virus
  • molecular clock
  • Bayesian phylogenetics
  • CORE PROMOTER
  • VERTICAL TRANSMISSION
  • MOLECULAR EVOLUTION
  • SEQUENCE VARIATION
  • C VIRUS
  • INFECTION
  • HISTORY
  • POPULATIONS
  • MUTATIONS
  • HBV

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