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

Abstract

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.

HBV DNA genome co-transfection procedure for the evaluation of relative fitness

“…In Argentina, it has been recently reported a high prevalence of sgtF1b in acute and chronic HBeAg positive infections followed by sgtA2, sgtF4 and sgtD. [ 13 – 15 ] Our results showed the same relative fitness between all of the genotype combinations, with the exception of the pair F1b-F4, which showed an increase of sgtF1b in the progeny. Additionally, when serial cycles of infection were simulated, results showed that the ratio between F1b and F4 kept moving in the direction of F1b predominance.…”

High prevalence of HBV infection, detection of subgenotypes F1b, A2, and D4, and differential risk factors among Mexican risk populations with low socioeconomic status

“…However, in this study, subgenotype F1b was notably present in 57% of the native cases (NOaxaca and NMichoacan) showing a closely genetic relatedness with other Latin American F1b strains. Other than the F1b cluster recently reported in Italy, this subgenotype that is more common among the western South American countries of Argentina and Chile has also been found in natives of Colombia and in Venezuela . Despite that HBV genotype H is most predominant in native Mexicans, the F1b strains found in Oaxaca were isolated from descendants of the ancient Mesoamerican Mixtecos.…”

“…The main reasons are the stratification of the population structure comprised of Native Amerindians and genetically-admixed Mestizos (Amerindian, Caucasian, and African lineages) and the concurrent high level of economic inequality. 12 Thereby, the endemic genotype H in Mexico 13 and the F1-F4 subgenotypes of Central and South America [14][15][16][17] correspondingly circulate among natives, rural, or urban, low-income class Mestizo subpopulations. Likewise, genotypes A, D, or B, C that circulate among urban populations of European descendants and Asian immigrants, respectively have been related to liver damage.…”

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations

“…In this study, we report evidence of an incomplete autophagy process induced by HBV sgts F1b and F4 replication in Huh-7 cells. These sgts, native from Latin America, are responsible for most of the new acute and chronic infections in our country [ 8 , 10 ], and have been scarcely studied so far.…”

“…Individuals infected with HBV sgt F1b seroconvert e antigen (HBeAg) later in life than those infected with sgt F4 [ 8 ]. In addition, recent studies have shown that sgt F1b is the main responsible of the new acute and chronic infections in Argentina [ 8 – 10 ]. Moreover, growing evidence has shown a close association of sgt F1b with more severe course of chronic HBV infections, and a high correlation between sgt F1b and the development of HCC exists among Alaska native people [ 11 – 13 ].…”