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

ELIZALDE, MM ..... VACCARO MI, FLICHMAN D

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2018 vol. 13 p. 1 - 16

1932-6203

HBV subgenotypes F1b and F4 replication inducesan incomplete autophagic process in hepatocytes: role of BCP and preCoremutations María Mercedes Elizalde 1,4,*, Paula Soledad Pérez 1,4, Ina Sevic 1,4,Daniel Grasso 2,4, Alejandro Ropolo 2,4, Luciana Barbini3,4, Rodolfo Héctor Campos 1,4, María Inés Vaccaro 2,4,Diego Martín Flichman 1,4<!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073697537 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}p.Default, li.Default, div.Default{mso-style-name:Default;mso-style-priority:99;mso-style-unhide:no;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;mso-layout-grid-align:none;text-autospace:none;font-size:12.0pt;font-family:"Arial",sans-serif;mso-fareast-font-family:Calibri;color:black;mso-ansi-language:ES-AR;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:8.0pt;line-height:107%;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.0in 1.0in 1.0in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->Hepatitis Bvirus (HBV) genotypes and mutants have been associated with differences inclinical and virological characteristics. Autophagy is a cellular process thatdegrades long-lived proteins and damaged organelles. Viruses have evolvedmechanisms to alter this process to survive in host cells. In this work, we studied themodulation of autophagy by the replication of HBV subgenotypes F1b and F4, and thenaturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4replication induced accumulation ofautophagosomes in hepatoma cells. However, no autophagic protein degradationwas observed, indicating a blockage of autophagic flux at later stages. Thisinhibition of autophagy flux might be due to an impairment of lysosomalacidification in hepatoma cells. Moreover, HBV-mediated autophagy modulationwas independent of the viral subgenotypes and enhanced in viruses with BCP andpreCore naturally occurring mutations. These results contribute to understandthe mechanisms by which different HBV variants contribute to the pathogenesisof HBV infections. In addition, this study is the first to describe the rolethat two highly prevalent naturally occurring mutations exert on the modulationof HBV-induced autophagy.<!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073697537 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:107%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}p.Default, li.Default, div.Default{mso-style-name:Default;mso-style-priority:99;mso-style-unhide:no;mso-style-parent:"";margin:0in;margin-bottom:.0001pt;mso-pagination:widow-orphan;mso-layout-grid-align:none;text-autospace:none;font-size:12.0pt;font-family:"Arial",sans-serif;mso-fareast-font-family:Calibri;color:black;mso-ansi-language:ES-AR;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-size:11.0pt;mso-ansi-font-size:11.0pt;mso-bidi-font-size:11.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-AR;}.MsoPapDefault{mso-style-type:export-only;margin-bottom:8.0pt;line-height:107%;}@page WordSection1{size:8.5in 11.0in;margin:1.0in 1.0in 1.0in 1.0in;mso-header-margin:.5in;mso-footer-margin:.5in;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->