Caracterización molecular y biológica del virus de la hepatitis C en pacientes con carcinoma hepatocelular
Chronic infection with hepatitis C virus (HCV) is a risk factor for hepatocellular carcinoma (HCC) development. CORE and NS5A have been associated with the modulation of potentially oncogenic cellular processes. In this work, HCV variants from different tissues of HCC patients were molecular and bio...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2109 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2109.dir/2109.PDF |
| Aporte de: |
| Sumario: | Chronic infection with hepatitis C virus (HCV) is a risk factor for hepatocellular carcinoma (HCC) development. CORE and NS5A have been associated with the modulation of potentially oncogenic cellular processes. In this work, HCV variants from different tissues of HCC patients were molecular and biologically characterized. The main genotype in the analyzed cohort (n=20) was HCV-1b. CORE and NS5A sequences from HCV-1b harbored molecular differences against patients without HCC. Compartmentalization was evaluated in five tumoral and non-tumoral liver tissue samples, by molecular cloning of CORE-E1-E2 region. Phylogenetic analyses and bayesian association test results showed compartmentalization of HCV in these tissues. This suggested the existence of a selection process of viral populations during hepatocarcinogenesis. In vitro expression of CORE protein stimulated cell proliferation, although this ability was not different amongst the analyzed variants. This finding indicated that the molecular differences between compartments would result from viral adaptation to different hepatic micro-environments, and would not be directly associated with the tumoral phenotype. In sum, this work contributes to the understanding of carcinogenesis mediated by HCV infection. |
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