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

Autor: María Mercedes Elizalde, Paula Soledad Pérez, Ina Sevic, Daniel Grasso, Alejandro Ropolo, Luciana Barbini, Rodolfo Héctor Campos, María Inés Vaccaro, Diego Martín Flichman
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS ONE, Vol 13, Iss 5, p e0197109 (2018)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0197109
Popis: 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.
Databáze: Directory of Open Access Journals
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