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Investigation of stop codons (TGA) recurrent in the Hepatitis C Virus NS5A region

Grant number: 13/02856-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2013
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Cintia Bittar Oliva
Grantee:Guilherme Rodrigues Fernandes Campos
Home 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

The hepatitis C virus (HCV) is a single strand positive RNA virus member of the Flaviviridae family. The infection leads to liver inflammation in general, asymptomatic, but when the infection becomes chronicle, it may cause problems like liver cirrhosis, fibrosis and hepatocellular carcinoma. It is believed that about 150 million people in the world suffer with this disease. The treatment is based on interferon and ribavirin, but in the serious cases, the liver transplant is needed. Due to the RNA genome, HCV has a high mutational rate, which classifies this virus in seven genotypes and different subtypes. Among its proteins, the NS5A shows to be important to act in the resistance of the virus to interferon as well as in the apoptotic processes of damaged cells, with a possible hole in the hepatocellular carcinogenesis. Recent studies found mutations that give rise to stop codons in the NS5A protein region recurrent in different patients. The presence of these stop codons would lead to early termination of the poliprotein translation preventing the translation of complete NS5A and as a consequence the following protein, the viral RNA dependent RNA polymerase NS5B. The TGA codon frequently leads to the stop of translation, however in some cases it may codify for a specific amino acid, the selenocystein. The aim of this study is to evaluate in cell culture the impact of the presence of the TGA codon in the position 111 (originally TGG) of the NS5A protein in the translation of this protein.