Study of the role of Hepatitis C virus proteins in the development of hepatocarcinoma

• Grant number: 12/01403-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2012
• End date: April 30, 2015
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Paula Rahal
• Grantee: Cintia Bittar Oliva
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Hepatitis C is a worldwide health problem with an estimated incidence of the infection by HCV of 2.2%, corresponding to 130 million people in the world. It is estimated that more than 75% of the infected persons develop chronic infection that could lead to cirrhosis and in some cases hepatocellular carcinoma (HCC). The HCC is the third major cause of death by cancer in adults. At first it was believed that the great incidence of HCC in HCV infected patients was an indirect consequence of the viral infection, however now it is believed that the viral proteins have a direct role in the hepatocarcinogenesis. Although some viral proteins already shown hepatocarcinogenic potential, there are still many questions and a lot to be studied to understand the role of Hepatitis C virus in cancer development. In this work we propose to use the culture of primary human hepatocytes to address the effect of the viral proteins NS2 and NS5A in cellular pathways that are important concerning cell transformation. The carcinogenic potential of NS5A protein has being studied, however due to its multifunctional characteristic and because all its functions are not well elucidated, this protein constitutes an important target for such studies. The NS2 protein is usually not studied in the context of hepatocarcinogenesis, however preliminary data indicates that it has an inhibitory potential of p53 protein which has a well known role in tumoral suppression. To understand how the viral proteins are modulating the cellular environment and what pathways are being affected, is extremely important to develop new treatments not only to overcome the viral infection but also that grant some protection to the development of a future chronic liver disease like hepotocarcinoma.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SHIMIZU, JACQUELINE FARINHA; PEREIRA, CARINA MACHADO; BITTAR, CINTIA; BATISTA, MARIANA NOGUEIRA; FERNANDES CAMPOS, GUILHERME RODRIGUES; DA SILVA, SUELY; OLIVEIRA CINTRA, ADELIA CRISTINA; ZOTHNER, CARSTEN; HARRIS, MARK; SAMPAIO, SUELY VILELA; et al. Multiple effects of toxins isolated from Crotalus durissus terrificus on the hepatitis C virus life cycle. PLoS One, v. 12, n. 11, NOV 15 2017. (12/01403-9, 11/00313-3, 13/03897-1)

SHIMIZU, JACQUELINE FARINHA; LIMA, CAROLINE SPRENGEL; PEREIRA, CARINA MACHADO; BITTAR, CINTIA; BATISTA, MARIANA NOGUEIRA; NAZARE, ANA CAROLINA; POLAQUINI, CARLOS ROBERTO; ZOTHNER, CARSTEN; HARRIS, MARK; RAHAL, PAULA; et al. Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry. SCIENTIFIC REPORTS, v. 7, NOV 23 2017. (12/01403-9, 14/22198-0, 13/03897-1, 14/05445-3)