title: Phylogeography and evolutionary history of hepatitis B virus genotype F in Brazil.
abstract: BACKGROUND
  Hepatitis B virus (HBV) genotype F (HBV/F) is considered to be indigenous to the Americas, but its emergence and spread in the continent remain unknown. Previously, only two HBV/F complete genome sequences from Brazil were available, limiting the contribution of Brazilian isolates to the phylogenetic studies of HBV/F. The present study was carried out to assess the proportion and geographic distributions of HBV/F subgenotypes in Brazil, to determine the full-length genomic sequences of HBV/F isolates from different Brazilian geographic regions, and to investigate the detailed evolutionary history and phylogeography of HBV/F in Brazil.
  
  
  METHODS
  Complete HBV/F genomes isolated from 12 Brazilian patients, representing the HBV/F subgenotypes circulating in Brazil, were sequenced and analyzed together with sequences retrieved from GenBank, using the Bayesian coalescent and phylogeographic framework.
  
  
  RESULTS
  Phylogenetic analysis using all Brazilian HBV/F S-gene sequences available in GenBank showed that HBV/F2a is found at higher frequencies countrywide and corresponds to all sequences isolated in the Brazilian Amazon Basin. In addition, the evolutionary analysis using complete genome sequences estimated an older median ancestral age for the Brazilian HBV/F2a compared to the Brazilian HBV/F1b and HBV/F4 subgenotypes, suggesting that HBV/F2a represents the original native HBV of Brazil. The phylogeographic patterns suggested a north-to-south flow of HBV/F2a from Venezuela to Brazil, whereas HBV/F1b and HBV/F4 strains appeared to have spread from Argentina to Brazil.
  
  
  CONCLUSIONS
  This study suggests a plausible route of introduction of HBV/F subgenotypes in Brazil and demonstrates the usefulness of recently developed computational tools for investigating the evolutionary history of HBV.
authors.affiliation: Laboratory of Molecular Virology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
authors.forename: Francisco C A
authors.initials: FC
authors.lastname: Mello
authors.forename: Oscar C
authors.initials: OC
authors.lastname: Araujo
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Lago
authors.forename: Ana Rita C
authors.initials: AR
authors.lastname: Motta-Castro
authors.forename: Marcia Terezinha B
authors.initials: MT
authors.lastname: Moraes
authors.forename: Selma A
authors.initials: SA
authors.lastname: Gomes
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Bello
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Araujo
mesh_terms: D001938:Brazil / Q000453:epidemiology; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D058974:Phylogeography; D017422:Sequence Analysis, DNA
chemical_list: D004279:DNA, Viral