HLA and NK Cell Inhibitory Receptor Genes in Resolving Hepatitis C Virus Infection

• DOI: 10.1126/science.1097670
• Publication Date: 2004-08-05T20:18:15Z
• Authors: Salim I. Khakoo; Chloe L. Thio; Maureen P. Martin; Collin R. Brooks; Xiaojiang Gao; Jacquie Astemborski; Jie Cheng; James J. Goedert; David Vlahov; Margaret Hilgartner; Steven Cox; Ann-Margeret Little; Graeme J. Alexander; Matthew E. Cramp; Stephen J. O'Brien; William M. C. Ros...; David L. Thomas; Mary Carrington
• Keywords: Adult; Male; 0301 basic medicine; Adolescent; 610; HLA-C Antigens; Hepacivirus; Ligands; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Receptors, KIR; 616; Medicine and Health Sciences; Humans; Blood Transfusion; Receptors, Immunologic; Child; Alleles; Immunology and Infectious Disease; Homozygote; Genetics and Genomics; Hepatitis C; 3. Good health; Black or African American; Killer Cells, Natural; Receptors, KIR2DL3; Receptors, KIR2DL1; Female

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 group1 (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.