The genetic diversity of hepatitis A genotype i in Bulgaria

Eleonora Cella, Elitsa N. Golkocheva-Markova, Diljana Trandeva-Bankova, Giulia Gregori, Roberto Bruni, Stefania Taffon, Michele Equestre, Angela Costantino, Silvia Spoto, Melissa Curtis, Anna Rita Ciccaglione, Massimo Ciccozzi, Silvia Angeletti

Research output: Contribution to journalArticlepeer-review


The purpose of this study was to analyze sequences of hepatitis A virus (HAV) Ia and Ib genotypes from Bulgarian patients to investigate the molecular epidemiology of HAV genotype I during the years 2012 to 2014. Around 105 serum samples were collected by the Department of Virology of the National Center of Infectious and Parasitic Diseases in Bulgaria. The sequenced region encompassed the VP1/2A region of HAV genome. The sequences obtained from the samples were 103. For the phylogenetic analyses, 5 datasets were built to investigate the viral gene in/out flow among distinct HAV subpopulations in different geographic areas and to build a Bayesian dated tree, Bayesian phylogenetic and migration pattern analyses were performed. HAV Ib Bulgarian sequences mostly grouped into a single clade. This indicates that the Bulgarian epidemic is partially compartmentalized. It originated from a limited number of viruses and then spread through fecal-oral local transmission. HAV Ia Bulgarian sequences were intermixed with European sequences, suggesting that an Ia epidemic is not restricted to Bulgaria but can affect other European countries. The time-scaled phylogeny reconstruction showed the root of the tree dating in 2008 for genotype Ib and in 1999 for genotype Ia with a second epidemic entrance in 2003. The Bayesian skyline plot for genotype Ib showed a slow but continuous growth, sustained by fecal-oral route transmission. For genotype Ia, there was an exponential growth followed by a plateau, which suggests better infection control. Bidirectional viral flow for Ib genotype, involving different Bulgarian areas, was observed, whereas a unidirectional flow fromSofia to Ihtiman for genotype Ia was highlighted, suggesting the fecal-oral transmission route for Ia.

Original languageEnglish
Article numbere9632
JournalMedicine (United States)
Issue number3
Publication statusPublished - Jan 1 2018


  • Bulgaria
  • genotype I
  • HAV
  • hepatitis A virus
  • phylodynamics
  • phylogeny

ASJC Scopus subject areas

  • Medicine(all)


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