Analysis of the relationship between "exhaustion" of T cells, variability of genes encoding hepatitis C virus (HCV) epitopes recognized by T cells, and the effect of antiviral therapy in patients with HCV infection and HIV-1/HCV co-infection.

Infection with the hepatitis C virus (HCV), causing hepatitis C (hepatitis C), affects approximately 170 million people worldwide. It is an important medical problem as it can lead to serious consequences such as liver failure and hepatocellular carcinoma. The hidden course of the infection, limited access to modern treatment, and the lack of a vaccine are the reasons for the constant spread of the virus around the world. In addition, co-infection with human immunodeficiency virus (HIV-1) and HCV is increasingly observed, worsening patient survival and the effectiveness of HCV antiviral therapy. The acquired immune response associated with cytotoxic T cell activity plays a very important role in the sequelae of hepatitis C virus (HCV) infection. Approximately 20-50% of the infected eliminate the infection spontaneously due to a strong, multispecific response of these cells. In contrast, chronic hepatitis C has shown a weak T-cell response to the virus of functional "exhaustion". There is a deterioration in the secretion of inflammatory factors (IFN-γ, TNF-α and IL-2), the ability to destroy infected cells and the ability to multiply T cells after the diagnosis of the virus. These disorders, caused by chronic stimulation of the immune system, progress with the duration of the infection and are characterized by an excess of specific PD-1 and Tim-3 receptors on the surface of T cells, including those specific for HCV, which "inhibit" the ability to multiply, destroy infected cells and the secretion of inflammatory factors. Moreover, there is an increased secretion of anti-inflammatory cytokines (mainly IL-10). So far, studies on T-cell "depletion" in HCV infection have relied on the mechanisms, degree of reversibility and impact of this phenomenon on the development of chronic infection, while no other sequelae are known. In particular, whether there a relationship between T cell "depletion" and the level of diversity of immunogenic protein fragments (epitopes) of the virus recognized by these cells. In addition, how antiviral therapy for HCV infection modifies T cell "depletion" The aim of this project is to determine: 1. the relationship between T cell "depletion" and the degree of heterogeneity of immunogenic fragments of hepatitis C virus proteins recognized by T cells in patients with infection HCV and with HIV-1 / HCV co-infection; 2. how treatment of chronic hepatitis C affects the degree of "depletion" of T cells in patients with HCV infection and HIV-1 / HCV co-infection.