Tracing back hepatitis B virus genotype D introduction and dissemination in South Brazil

Abstract

Hepatitis B virus (HBV) infection is widespread and it is considered a major health problem in the world. HBV is classified into genotypes and subgenotypes. HBV genotype D (HBV-D) has been detected worldwide with high prevalence in some specific regions from Europe and South America. In Brazil, this genotype is very frequent in the South region and its introduction and dissemination have been associated with European immigration (mainly Italian). The present study aimed to trace back the introduction and dissemination of HBV-D in South Brazil. Fifty-two chronic hepatitis B patients from two cities with an early history of Italian immigration in South Brazil were selected for the present study. HBV-DNA was detected, quantified and a partial genomic region (S/P overlapped genes) was amplified by PCR and sequenced for the determination of HBV genotypes/subgenotypes. HBV complete genome sequences of some selected samples were further obtained. Bayesian coalescent analyses were performed to estimate the HBV-D evolutionary dynamics. Phylogenetic analysis demonstrated the occurrence of three genotypes according the tree topology: HBV-D (n = 49; 94.2%), HBV-A (n = 2; 3.9%) and HBV-G (n = 1; 1.9%). In addition, HBV-D presented three subgenotypes: HBV-D3 (n = 39; 79.6%), HBV-D2 (n = 8; 16.3%), and HBV-D1 (n = 2; 4.1%). The Bayesian coalescent analysis demonstrated that the HBV-D was introduced in the 20th century. HBV-D3 was the first to be introduced in South Brazil, probably between 1904 and 1942. HBV-D2 and HBV-D1 were introduced later; HBV-D2 between 1946 and 1953 and HBV-D1 between 1954 and 1969. HBV-D3 spread at a high rate from the 1920s to the 1980s, while HBV-D2 showed a slower growth from the 1960s to the 1990s and HBV-D1 infections demonstrated low and constant population size across time. After the 2000s, a stationary growth was detected for all these three-D subgenotypes. HBV-D showed a high prevalence in South Brazil and this is possibly associated with the first introduction and dissemination of HBV-D3 at the beginning of the 20th century.