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Home / Publicações / Proteomic changes in HEK-293 cells induced by hepatitis delta virus replication

Proteomic changes in HEK-293 cells induced by hepatitis delta virus replication

  • Autores: Coelho AV, Cunha C, Mendes M, Pérez-Hernandez D, Vázquez J
  • Ano de Publicação: 2013
  • Journal: Journal of Proteomics
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/23770296

Hepatitis delta virus (HDV) infection greatly increases the risk of hepatocellular carcinoma in hepatitis B virus chronically infected patients. HDV is highly dependent on host factors for accomplishment of the replication cycle. However, these factors are largely unknown and the mechanisms involved in the pathogenicity of the virus still remain elusive.

Here, we made use of the HEK-293 cell line, which was engineered in order to mimic HDV replication. Five different proteomes were analyzed and compared using a MS-based quantitative proteomics approach by (18)O/(16)O stable isotope labeling. About 3000 proteins were quantified and 89 found to be differentially expressed as a consequence HDV RNA replication.

The down-regulation of p53 , HSPE, and ELAV as well as the up-regulation of Transportin 1 , EIF3D, and Cofilin 1 were validated by Western blot. A systems biology approach was additionally used to analyze altered pathways and networks. The G2/M DNA damage checkpoint and pyruvate metabolism were among the most affected pathways, and Cancer was the most likely disease associated to HDV replication.

Western blot analysis allowed identifying 14-3-3 σ interactor as down-regulated protein acting in the G2/M cell cycle control checkpoint. This evidence supports deregulation of G2/M checkpoint as a possible mechanism involved in the promotion of HDV associated hepatocellular carcinoma.

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About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

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