Compartmentalization of hepatitis C virus variants in patients with hepatocellular carcinoma

Authors
Pérez, Paula Soledad; Di Lello, Federico Alejandro; Mullen, Eduardo; Galdame, Omar; Livellara, Beatriz I.; Gadano, Adrián Carlos; Campos, Rodolfo Hector; Flichman, Diego Martin
Publication Year
2017
Language
English
Format
article
Status
Published version
Description
Chronic Hepatitis C Virus (HCV) infection is a major risk for hepatocellular carcinoma (HCC) development. HCV Core protein has been associated with the modulation of potentially oncogenic cellular processes and E2 protein has been useful in evolutive studies to analyze the diversity of HCV. Thus, the aim of this study was to evaluate HCV compartmentalization in tumoral, non-tumoral liver tissue and serum and to identify viral mutations potentially involved in carcinogenesis. Samples were obtained from four patients with HCC who underwent liver transplantation. Core and E2 were amplified, cloned and sequenced. Phylogenies and BaTS Test were performed to analyze viral compartmentalization and a signature sequence analysis was conducted by VESPA. The likelihood and Bayesian phylogenies showed a wide degree of compartmentalization in the different patients, ranging from total clustering to a more scattered pattern with small groups. Nevertheless, the association test showed compartmentalization for the three compartments and both viral regions tested in all the patients. Signature amino acid pattern supported the compartmentalization in three of the cases for E2 protein and in two of them for Core. Changes observed in Core included polymorphism R70Q/H previously associated with HCC. In conclusion, evidence of HCV compartmentalization in the liver of HCC patients was provided and further biological characterization of these variants may contribute to the understanding of carcinogenesis mediated by HCV infection.
Fil: Pérez, Paula Soledad. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Mullen, Eduardo. Hospital Italiano; Argentina
Fil: Galdame, Omar. Hospital Italiano; Argentina
Fil: Livellara, Beatriz I.. Hospital Italiano; Argentina
Fil: Gadano, Adrián Carlos. Hospital Italiano; Argentina
Fil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Subject
COMPARTMENTALIZATION
HEPATITIS C VIRUS
HEPATOCELLULAR CARCINOMA
LIVER TRANSPLANT
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/47702