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Analysis of polymorphisms, gene expression and serum levels of IL-18,IL18BP and IFN-gamma in chronic HCV infection and spontaneous clearance

Grant number: 12/20248-4
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2013
Effective date (End): December 31, 2014
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:João Renato Rebello Pinho
Grantee:Paola Lara Faria
Home Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hepatitis C Virus (HCV) infection has a worldwide impact and it is estimated that over 170 million people are infected with this virus, many of them suffering from chronic hepatitis. About 80% of patients with acute HCV infection do not eliminate the virus and progress to a chronic infection. However, 20% of those who come in contact with the virus spontaneously resolve infection after mounting an effective immune response. In this way, the course of HCV infection is determined by the innate and adaptive immune responses of the host. Interleukin - 18 (IL-18) is an important pro-inflammatory cytokine in immune response and acts synergistically with IL-12 to induce the expression of IFN- ³ by T and natural killer cells. Although IL-18 plays a key role in host defense against intracellular pathogens, an excess of IL-18 can induce topic or systemic damage in the host. One way to control this cytokine activity is by IL-18 binding protein (IL18BP), which is a natural antagonist of IL-18 preventing that it will exert its biological activity. Studies have shown that individuals infected with HCV have elevated plasma levels of IL-18 and IL18BP. Therefore, the aims of this study are 1) to genotype single nucleotide polymorphisms (SNPs) located in the gene for IL-18 (rs1946518 and rs187238) and IL18BP (rs2298455 and rs3750912); 2) quantify the expression of their mRNA; 3) and finally, to determine the serum levels of cytokines and IFN- ³. The analysis of these data will allow comparing the profile of groups with spontaneous resolution and with chronic HCV infection.