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HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection |
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| Authors: | Khakoo Salim I Thio Chloe L Martin Maureen P Brooks Collin R Gao Xiaojiang Astemborski Jacquie Cheng Jie Goedert James J Vlahov David Hilgartner Margaret Cox Steven Little Ann-Margeret Alexander Graeme J Cramp Matthew E O'Brien Stephen J Rosenberg William M C Thomas David L Carrington Mary |
| Affiliation: | Liver Group, Division of Infection, Inflammation, and Repair, Southampton University, Southampton 5016 6YD, UK. sik@soton.ac.uk |
| Abstract: | Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV. |
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