title: Genomic analysis of hepatitis B virus reveals antigen state and genotype as sources of evolutionary rate variation.
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.
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK. a.g.l.harrison@gmail.com
authors.forename: Abby
authors.initials: A
authors.lastname: Harrison
authors.forename: Philippe
authors.initials: P
authors.lastname: Lemey
authors.forename: Matthew
authors.initials: M
authors.lastname: Hurles
authors.forename: Chris
authors.initials: C
authors.lastname: Moyes
authors.forename: Susanne
authors.initials: S
authors.lastname: Horn
authors.forename: Jan
authors.initials: J
authors.lastname: Pryor
authors.forename: Joji
authors.initials: J
authors.lastname: Malani
authors.forename: Mathias
authors.initials: M
authors.lastname: Supuri
authors.forename: Andrew
authors.initials: A
authors.lastname: Masta
authors.forename: Burentau
authors.initials: B
authors.lastname: Teriboriki
authors.forename: Tebuka
authors.initials: T
authors.lastname: Toatu
authors.forename: David
authors.initials: D
authors.lastname: Penny
authors.forename: Andrew
authors.initials: A
authors.lastname: Rambaut
authors.forename: Beth
authors.initials: B
authors.lastname: Shapiro
mesh_terms: D001499:Bayes Theorem; D004279:DNA, Viral / Q000235:genetics*; D030541:Databases, Genetic; D019143:Evolution, Molecular; D016679:Genome, Viral / Q000235:genetics*; D006509:Hepatitis B / Q000453:epidemiology; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008957:Models, Genetic; D010139:Pacific Islands / Q000453:epidemiology; D010802:Phylogeny; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens