Mutaciones K130M V131I en la proteína X del virus de la hepatitis B y sus implicancias en los mecanismos de patogenia de la infección crónica

The hepatitis B virus X protein (HBV-X) is associated with the pathogenesis of liver disease in chronic HBV infection. BCP mutations, which occur during the natural history of infection, affect HBV-X at 130-131 amino acids. The role of these mutations on the biological activity of the protein is unk...

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Autor principal: Elizalde, María Mercedes
Otros Autores: Flichman, Diego
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2016
Materias:
HBV
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1209
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1209.dir/1209.PDF
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Sumario:The hepatitis B virus X protein (HBV-X) is associated with the pathogenesis of liver disease in chronic HBV infection. BCP mutations, which occur during the natural history of infection, affect HBV-X at 130-131 amino acids. The role of these mutations on the biological activity of the protein is unknown. The aim of this Thesis was to analyze the impact of the presence of different amino acids at 130-131 of HBV-X on its biological activity. Wild type and mutated X gene of subgenotypes F1b and F4 were cloned and the different HBV-X were expressed in human hepatoma cell lines. The expression of the proteins increased cell mortality through the apoptotic process and the differential modulation in the expression of the Bcl-2 family proteins. Furthermore, the expression of HBV-X of both subgenotypes induced the autophagy of hepatocytes. These results describe the molecular mechanisms whereby HBV-X variants contribute to the pathogenesis in the infected liver and promote the characterization of genotype F, responsible for most of the hepatitis in the region.