X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy
The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130–131 positions. The role o...
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2017
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01681702_v242_n_p156_Elizalde http://hdl.handle.net/20.500.12110/paper_01681702_v242_n_p156_Elizalde |
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paper:paper_01681702_v242_n_p156_Elizalde2023-06-08T15:17:40Z X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy Apoptosis Autophagy Basal core promoter mutation Genotype F Hepatitis B virus Hepatitis B virus X protein cell DNA hepatitis B virus X protein protein Bax protein bcl 2 protein bcl x apoptosis Article autophagosome autophagy cell membrane cell nucleus membrane cell structure cell vacuole chromatin condensation controlled study fluorescence microscopy hepatitis B Hepatitis B virus Hepatitis B virus genotype F hepatoma cell human human cell liver cell nonhuman priority journal signal transduction transient expression transient transfection wild type The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130–131 positions. The role of these mutations on HBV-X biological activity remains largely unknown. The aim of this study was to analyze the impact of the presence of different amino acids at 130–131 positions of HBV-X on the biological activity of the protein. Transient expression of wild type and mutant F1b and F4 HBV-X increased cell mortality by the induction of apoptosis in human hepatoma cells. The wild type and mutant HBV-X differentially modulate the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2 and Bcl-X) regulatory proteins of the Bcl-2 family. Furthermore, the expression of HBV-X variants of both subgenotypes induced autophagy of human tumoral hepatocytes. In conclusion, HBV-X variants of the Latin American HBV F genotype promotes human hepatocytes death by the induction of apoptosis and autophagy. The results of this work describe some of the molecular mechanisms by which HBV-X variants contribute to the pathogenesis of liver diseases in the infected liver and help to the biological characterization of genotype F, responsible of the majority of HBV infections in Argentina. © 2017 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01681702_v242_n_p156_Elizalde http://hdl.handle.net/20.500.12110/paper_01681702_v242_n_p156_Elizalde |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Apoptosis Autophagy Basal core promoter mutation Genotype F Hepatitis B virus Hepatitis B virus X protein cell DNA hepatitis B virus X protein protein Bax protein bcl 2 protein bcl x apoptosis Article autophagosome autophagy cell membrane cell nucleus membrane cell structure cell vacuole chromatin condensation controlled study fluorescence microscopy hepatitis B Hepatitis B virus Hepatitis B virus genotype F hepatoma cell human human cell liver cell nonhuman priority journal signal transduction transient expression transient transfection wild type |
| spellingShingle |
Apoptosis Autophagy Basal core promoter mutation Genotype F Hepatitis B virus Hepatitis B virus X protein cell DNA hepatitis B virus X protein protein Bax protein bcl 2 protein bcl x apoptosis Article autophagosome autophagy cell membrane cell nucleus membrane cell structure cell vacuole chromatin condensation controlled study fluorescence microscopy hepatitis B Hepatitis B virus Hepatitis B virus genotype F hepatoma cell human human cell liver cell nonhuman priority journal signal transduction transient expression transient transfection wild type X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| topic_facet |
Apoptosis Autophagy Basal core promoter mutation Genotype F Hepatitis B virus Hepatitis B virus X protein cell DNA hepatitis B virus X protein protein Bax protein bcl 2 protein bcl x apoptosis Article autophagosome autophagy cell membrane cell nucleus membrane cell structure cell vacuole chromatin condensation controlled study fluorescence microscopy hepatitis B Hepatitis B virus Hepatitis B virus genotype F hepatoma cell human human cell liver cell nonhuman priority journal signal transduction transient expression transient transfection wild type |
| description |
The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130–131 positions. The role of these mutations on HBV-X biological activity remains largely unknown. The aim of this study was to analyze the impact of the presence of different amino acids at 130–131 positions of HBV-X on the biological activity of the protein. Transient expression of wild type and mutant F1b and F4 HBV-X increased cell mortality by the induction of apoptosis in human hepatoma cells. The wild type and mutant HBV-X differentially modulate the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2 and Bcl-X) regulatory proteins of the Bcl-2 family. Furthermore, the expression of HBV-X variants of both subgenotypes induced autophagy of human tumoral hepatocytes. In conclusion, HBV-X variants of the Latin American HBV F genotype promotes human hepatocytes death by the induction of apoptosis and autophagy. The results of this work describe some of the molecular mechanisms by which HBV-X variants contribute to the pathogenesis of liver diseases in the infected liver and help to the biological characterization of genotype F, responsible of the majority of HBV infections in Argentina. © 2017 |
| title |
X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| title_short |
X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| title_full |
X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| title_fullStr |
X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| title_full_unstemmed |
X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| title_sort |
x protein variants of the autochthonous latin american hepatitis b virus f genotype promotes human hepatocyte death by the induction of apoptosis and autophagy |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01681702_v242_n_p156_Elizalde http://hdl.handle.net/20.500.12110/paper_01681702_v242_n_p156_Elizalde |
| _version_ |
1768544362014179328 |