Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

<div><p>Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.</p></div

MCCT for subgenotype F4.

<p>Maximum clade credibility tree (MCCT) performed by calibration with the terminal nodes for complete genome of acute subgenotype F4 samples. The MCCT presents for each node plots of its correspondent posterior probability. Labels I_F4-III_F4 represent the clusters found in the circulating strains. The scale at the bottom of the tree represents time (years).</p

MCCT for subgenotype F1b.

<p>Maximum clade credibility tree (MCCT) performed by calibration with the terminal nodes for complete genome of acute subgenotype F1b samples. The MCCT presents for each node plots of its correspondent posterior probability. Labels I_F1b-IV_F1b represent the clusters found in the circulating strains. The scale at the bottom of the tree represents time (years).</p

Subgenotype distribution of the acute isolates.

<p>Maximum-likelihood phylogenetic tree performed with the PhyML (v3.0) program constructed on the complete genome sequences including fifty-five sequences of symptomatic acute HBV isolates from the city of Buenos Aires (marked with ♦) and reference sequences retrieved from GenBank, indicated by their accession numbers. The numbers at each node correspond to bootstrap values obtained with 1000 replicates. The scale bar indicates the genetic distances.</p

Co-estimation of substitution rates and tMRCAs¹.

<p>Co-estimation of substitution rates and tMRCAs<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159509#t001fn001" target="_blank">¹</a>.</p