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“Hepatitis C virus (HCV) is a common chronic viral infection with only a minority of individuals exposed to HCV infection being able Selleck Antidiabetic Compound Library to resolve infection spontaneously. Clearance of HCV is dependent on a successful immune response, which likely involves T cells, B cells, dendritic cells, and also natural killer cells (NK) cells.1 Consistent with a broad immune response being important, polymorphisms of both the innate and adaptive immune system are associated with spontaneous resolution of HCV infection.2

Recent work has highlighted that polymorphisms in the Interleukin-28B (IL28B) gene (interferon [IFN]-λ3) are strongly associated with both spontaneous resolution of HCV infection and also resolution of infection with pegylated interferon Seliciclib research buy and ribavirin. 2, 3, 4, 5, 6 and 7 Similarly, the killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen class I ligands have also been implicated in spontaneous and treatment-induced resolution of HCV infection. 8, 9, 10 and 11 In particular, KIR2DL3 and its ligands, the group 1 HLA-C allotypes (HLA-C1), are protective against chronic HCV infection and, hence, are beneficial factors in outcome following exposure to HCV. A

minority of long-term injection drug users (IDU) demonstrate apparent resistance to HCV infection and remain seronegative and aviremic despite likely repeated exposure to HCV through the sharing of drug injection equipment. These exposed but uninfected (EU) IDU cases have been shown to have detectable HCV-specific T-cell responses, indicating their exposure to HCV infection.12 and 13 They also have increased NK cell activity.14 Consistent

with this, we have recently shown that, similar to conventional spontaneous resolvers (SR), the combination of KIR2DL3 and HLA-C1 is also over-represented in the exposed seronegative aviremic population. 10 PAK5 Additionally, both groups of protected individuals have an increased frequency of a functional interleukin-12 (IL-12) polymorphism as compared with chronically infected individuals. 15 and 16 To date, the protective effect of IL28B in this subgroup of individuals has not been investigated. Furthermore, it is not well understood whether protective polymorphisms in the immune system work together to increase protection against chronic HCV infection or whether these components of the innate immune system act independently. The aim of this study was therefore to determine whether the EU population have a protective IL28B genotype and to determine how protective IL28B and KIR:HLA-C polymorphisms may interact to influence the outcome of HCV infection in untreated individuals. Three hundred ninety-seven patients (74 exposed uninfected, 89 SR, and 234 chronically infected patients) were studied for the distribution of the IL28B.