Genetic variability of hepatitis B virus in acute and in different phases of chronic infection in Brazil

Author:

Lago Barbara Vieira,Portilho Moyra Machado,Mello Vinicius Motta,De Sousa Paulo Sergio Fonseca,Angelice Giovana Paula,Marques Bianca Cristina Leires,da Silva Andrade Larissa Tropiano,Marques Vanessa Alves,Lewis-Ximenez Lia Laura,Mello Francisco Campello do Amaral,Villar Livia Melo

Abstract

AbstractThe selection pressure imposed by the host immune system impacts on hepatitis B virus (HBV) variability. This study evaluates HBV genetic diversity, nucleos(t)ide analogs resistance and HBsAg escape mutations in HBV patients under distinct selective pressures. One hundred and thirteen individuals in different phases of HBV infection were included: 13 HBeAg-positive chronic infection, 9 HBeAg-positive chronic hepatitis, 47 HBeAg-negative chronic infection (ENI), 29 HBeAg-negative chronic hepatitis (ENH) and 15 acute infected individuals. Samples were PCR amplified, sequenced and genetically analyzed for the overlapping POL/S genes. Most HBV carriers presented genotype A (84/113; 74.3%), subgenotype A1 (67/84; 79.7%), irrespective of group, followed by genotypes D (20/113; 17.7%), F (8/113; 7.1%) and E (1/113; 0.9%). Clinically relevant mutations in polymerase (tL180M/M204V) and in the Major Hydrophilic Region of HBsAg (sY100C, T118A/M, sM133T, sD144A and sG145R) were observed. Our findings, however, indicated that most polymorphic sites were located in the cytosolic loops (CYL1-2) and transmembrane domain 4 (TMD4) of HBsAg. Lower viral loads and higher HBV genetic diversity were observed in ENI and ENH groups (p < 0.001), suggesting that these groups are subjected to a higher selective pressure. Our results provide information on the molecular characteristics of HBV in a diverse clinical setting, and may guide future studies on the balance of HBV quasispecies at different stages of infection.

Funder

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Springer Science and Business Media LLC

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