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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todo:paper_01681702_v242_n_p156_Elizalde2023-10-03T15:06:16Z X protein variants of the autochthonous Latin American hepatitis B virus F genotype promotes human hepatocyte death by the induction of apoptosis and autophagy Elizalde, M.M. Campos, R.H. Barbini, L. 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 JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01681702_v242_n_p156_Elizalde |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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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 Elizalde, M.M. Campos, R.H. Barbini, L. 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 |
| format |
JOUR |
| author |
Elizalde, M.M. Campos, R.H. Barbini, L. |
| author_facet |
Elizalde, M.M. Campos, R.H. Barbini, L. |
| author_sort |
Elizalde, M.M. |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_01681702_v242_n_p156_Elizalde |
| work_keys_str_mv |
AT elizaldemm xproteinvariantsoftheautochthonouslatinamericanhepatitisbvirusfgenotypepromoteshumanhepatocytedeathbytheinductionofapoptosisandautophagy AT camposrh xproteinvariantsoftheautochthonouslatinamericanhepatitisbvirusfgenotypepromoteshumanhepatocytedeathbytheinductionofapoptosisandautophagy AT barbinil xproteinvariantsoftheautochthonouslatinamericanhepatitisbvirusfgenotypepromoteshumanhepatocytedeathbytheinductionofapoptosisandautophagy |
| _version_ |
1807315393817083904 |