Phylogeography of hepatitis B virus: The role of Portugal in the early dissemination of HBV worldwide

PLoS One. 2022 Dec 22;17(12):e0276618. doi: 10.1371/journal.pone.0276618. eCollection 2022.


In Portugal, the genetic diversity, origin of HBV and the Portuguese role in the dissemination of HBV worldwide were never investigated. In this work, we studied the epidemic history and transmission dynamics of HBV genotypes that are endemic in Portugal. HBV pol gene was sequenced from 130 patients followed in Lisbon. HBV genotype A was the most prevalent (n = 54, 41.5%), followed by D (n = 44, 33.8%), and E (n = 32, 24.6%). Spatio-temporal evolutionary dynamics was reconstructed in BEAST using a Bayesian Markov Chain Monte Carlo method, with a GTR nucleotide substitution model, an uncorrelated lognormal relaxed molecular clock model, a Bayesian skyline plot, and a continuous diffusion model. HBV subgenotype D4 was the first to be introduced in Portugal around 1857 (HPD 95% 1699-1931) followed by D3 and A2 a few decades later. HBV genotype E and subgenotype A1 were introduced in Portugal later, almost simultaneously. Our results indicate a very important role of Portugal in the exportation of subgenotypes D4 and A2 to Brazil and Cape Verde, respectively, in the beginning of the XX century. This work clarifies the epidemiological history of HBV in Portugal and provides new insights in the early and global epidemic history of this virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • DNA, Viral / genetics
  • Genotype
  • Hepatitis B virus* / genetics
  • Hepatitis B* / epidemiology
  • Humans
  • Phylogeny
  • Phylogeography
  • Portugal / epidemiology


  • DNA, Viral

Grants and funding

This work was performed in the context of Rute Marcelino PhD study, whose student’s fellowship (SFRH/BD/99507/2014) was supported by the Portuguese Agency for Scientific Research, Fundação para a Ciência e Tecnologia (FCT), POCH program, Portugal 2020, and European Union/Social European Fund (FSE). This work was also supported by FCT through funds of AA's projects GHTM-UID/Multi/04413/2013 and GHTM-UID/04413/2020 and also NT's projects UIDB/04138/2020 and UIDP/04138/2020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.