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

• Published in: Science (American Association for the Advancement of Science) Vol. 305; no. 5685; pp. 872 - 874
• Main 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., William M. C. Rosenberg, Thomas, David L., Carrington, Mary
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 06-08-2004; The American Association for the Advancement of Science
• Subjects: Adolescent; Adult; African Americans; African Americans - genetics; Alleles; Antigens; Biological and medical sciences; Blood Transfusion; Cells; Child; Cohort Studies; Drug Use; European Continental Ancestry Group - genetics; Female; Genes; Genetic aspects; Genotypes; Hepacivirus - immunology; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C - genetics; Hepatitis C - immunology; Hepatitis C - transmission; Hepatitis C - virology; Hepatitis C virus; HLA antigens; HLA C antigens; HLA-C Antigens - genetics; HLA-C Antigens - immunology; HLA-C Antigens - metabolism; Homozygote; Human viral diseases; Humans; Immune system; Infections; Infectious diseases; Killer Cells, Natural - immunology; Ligands; Male; Medical sciences; Natural killer cells; Physiological aspects; Protective effects; Receptors; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Receptors, KIR; Receptors, KIR2DL1; Receptors, KIR2DL3; Regression Analysis; Viral diseases; Viral hepatitis; Viruses; Whites; Human; HLA-System; Immune response; Major histocompatibility system; Hepatic disease; Cell cell interaction; Cellular immunity; Host virus relation; Infection; Virus; Natural killer cell; Viral disease; Digestive diseases; Flaviviridae; Hepatitis C virus; Hepacivirus; Viral hepatitis C; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1097670

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.