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 19th and 20th 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.
Highlights
Despite the availability of an effective vaccine and potent antiviral treatment, hepatitis B virus (HBV) infection remains a major public health issue, affecting 257 million people worldwide [1, 2]
HBV genomes were classified as D1 (n = 1), D2 (n = 10), D3 (n = 27), and D4 (n = 1) (Fig 1)
The serological subtypes were determined as follows: subgenotype D1 strain was classified as ayw2, D2 as 90% ayw3 and 10% ayw4, D3 as 78% ayw2 and 22% ayw3, and the D4 strain as ayw2
Summary
Despite the availability of an effective vaccine and potent antiviral treatment, hepatitis B virus (HBV) infection remains a major public health issue, affecting 257 million people worldwide [1, 2]. The significant diversity within specific HBV genotypes has led to further classification into numerous subgenotypes [10, 11]. HBV genotypes and subgenotypes have distinct geographic distributions and are associated with differences in disease progression, response to antiviral therapy, and clinical outcome [12,13,14,15]. HBV/D is distributed worldwide with predominance in Southeastern Europe, the Mediterranean Basin, the Middle East, and the Indian sub-continent [16]. It has the shortest genome (3,182 nt) and is characterized by a 33 nt deletion at the beginning of the pre-S1 region. Relative to HBV/A, HBV/D is associated with poorer clinical outcomes for cirrhosis and hepatocellular carcinoma and lower response to interferon alpha [14]
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