The Impact of Negative Regulation on T cell Immunity During Chronic Hepatitis C Virus Infections: A study on immunity of liver and peripheral blood

The hepatitis C virus (HCV) is very successful in establishing persistent infections by evading the immune system and predominantly infecting hepatocytes. HCV was known as non-A non-B hepatitis since the 1970’s and identified as a unique virus in 1989 1. HCV is a single-strand positive sense RNA virus belonging to the Flaviviridae family, has six major genotypes (1 to 6) and more than 100 subtypes have been identified. The single ~9600 nucleotide RNA molecule carries one open reading frame encoding for the structural proteins core, envelope 1 (E1), envelope 2 (E2), p7, and 6 non-structural proteins (NS) needed for replication (NS2, NS3, NS4a, NS4b, NS5a and NS5b). The current model of HCV infection suggests that after entering circulation, HCV is transported to the liver via lipoproteins where HCV binds to low density lipoprotein receptors, and possibly DC-sign and other receptors on hepatocytes, followed by viral entry in a clathrin-dependent endocytic process requiring interaction between the viral envelope with cell surface tetraspanin CD81, scavenger receptor type B class I, and the tight junction proteins claudin-1 and occludin (reviewed in 2). Controversy exists whether HCV directly impairs immune cell functions by infecting these cells. However, following infection, innate immunity and the HCV-specific immune response mediated via T cells are functionally impaired, and unable to eliminate the HCV in the majority of individuals 3-6. Only a minority of infected patients are able to clear HCV spontaneously, and about 80% develop a chronic infection with viral replication primarily occurring in the liver 7. It is estimated that globally 120 to 170 million patients are persistently infected with HCV.

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