info:eu-repo/semantics/article
HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations
Fecha
2018-05Registro en:
Elizalde, Maria Mercedes; Pérez, Paula Soledad; Sevic, Ina; Grasso, Daniel Hector; Ropolo, Alejandro Javier; et al.; HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations; Public Library of Science; Plos One; 13; 5; 5-2018; 1-16
1932-6203
CONICET Digital
CONICET
Autor
Elizalde, Maria Mercedes
Pérez, Paula Soledad
Sevic, Ina
Grasso, Daniel Hector
Ropolo, Alejandro Javier
Barbini, Luciana Fernanda
Campos, Rodolfo Hector
Vaccaro, Maria Ines
Flichman, Diego Martin
Resumen
Hepatitis B virus (HBV) genotypes and mutants have been associated with differences in clinical and virological characteristics. Autophagy is a cellular process that degrades long-lived proteins and damaged organelles. Viruses have evolved mechanisms to alter this process to survive in host cells. In this work, we studied the modulation of autophagy by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4 replication induced accumulation of autophagosomes in hepatoma cells. However, no autophagic protein degradation was observed, indicating a blockage of autophagic flux at later stages. This inhibition of autophagy flux might be due to an impairment of lysosomal acidification in hepatoma cells. Moreover, HBV-mediated autophagy modulation was independent of the viral subgenotypes and enhanced in viruses with BCP and preCore naturally occurring mutations. These results contribute to understand the mechanisms by which different HBV variants contribute to the pathogenesis of HBV infections. In addition, this study is the first to describe the role that two highly prevalent naturally occurring mutations exert on the modulation of HBV-induced autophagy.