Reconstruction of the spatial and temporal dynamics of hepatitis B virus genotype D in the Americas

Abstract

Hepatitis B virus (HBV) genotype D (HBV/D) is globally widespread, and ten subgenotypes (D1 to D10) showing distinct geographic distributions have been described to date. The evolutionary history of HBV/D and its subgenotypes, for which few complete genome sequences are available, in the Americas is not well understood. The main objective of the current study was to determine the full-length genomic sequences of HBV/D isolates from Brazil and frequency, origin and spread of HBV/D subgenotypes in the Americas. Complete HBV/D genomes isolated from 39 Brazilian patients infected with subgenotypes D1 (n = 1), D2 (n = 10), D3 (n = 27), and D4 (n = 1) were sequenced and analyzed together with reference sequences using the Bayesian coalescent and phylogeographic framework. A search for HBV/D sequences available in GenBank revealed 209 complete and 926 partial genomes from American countries (Argentina, Brazil, Canada, Chile, Colombia, Cuba, Haiti, Martinique, Mexico, USA and Venezuela), with the major circulating subgenotypes identified as D1 (26%), D2 (17%), D3 (36%), D4 (21%), and D7 (1%) within the continent. The detailed evolutionary history of HBV/D in the Americas was investigated by using different evolutionary time scales. Spatiotemporal reconstruction analyses using short-term substitution rates suggested times of the most recent common ancestor for the American HBV/D subgenotypes coincident with mass migratory movements to Americas during the 19 th and 20 th centuries. In particular, significant linkages between Argentina and Syria (D1), Brazil and Central/Eastern Europe (D2), USA and India (D2), and Brazil and Southern Europe (D3) were estimated, consistent with historical and epidemiological data.

Comprehensive Analysis of Clinically Significant Hepatitis B Virus Mutations in Relation to Genotype, Subgenotype and Geographic Region

“…Since HBV replication involves an error-prone reverse transcription step, nucleotide substitution rates are higher than those for other DNA viruses. The estimated HBV mutation rates are reported to range from 10 –4 to 10 –6 substitutions/site/year ( Zehender et al, 2014 ; Paraskevis et al, 2015 ; Spitz et al, 2019 ). This high substitution rate allows HBV to evolve rapidly and adapt to changes in the host environment, leading to the emergence of mutations with important implications for prevention, diagnosis, treatment, and prognosis of infection.…”

Analysis of Hepatitis B Virus Genotype D in Greenland Suggests the Presence of a Novel Quasi-Subgenotype

“…The more closely related subgenotype D2 may have an origin from the Middle East (Kostaki et al, 2018 ) or Southern Europe (Spitz et al, 2019 ). The use of ancient HBV DNA allowed us to estimate a Greenland HBV/D TMRCA range of 37–1138 CE.…”

Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies

“…In both HBV CD1 and CD2 recombinant genomes, the 'C fragment' and 'D fragment' were genetically close to subgenotype C2 and D4, respectively. HBV/D4 isolates were mainly reported in South America and the Pacific islands [14]. The only report of HBV/D4 in Asia was in northeast India [23].…”

“…Generally, the mutation definition and analysis were performed as previously described [13]. The whole genome, including S gene, PreC/C gene, reverse transcriptase (RT), X gene and basal core promoter (BCP) were under [14,15]. Nucleotide sequences of datasets in this study and reference HBV sequences were analyzed using the MEGA 7.0 software and Mutation Reporter Tool [16].…”