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

American Association for the Advancement of Science (AAAS) - Tập 305 Số 5685 - Trang 872-874 - 2004
Salim I. Khakoo1,2,3,4,5, Chloe L. Thio1,2,3,4,5, Maureen P. Martin1,3,4,5, Collin Brooks1,2,3,4,5, Xiaojiang Gao1,3,4,5, Jacquie Astemborski1,2,3,4,5, Jie Cheng1,3,4,5, James J. Goedert1,2,4,5, David Vlahov1,2,3,4,5, Margaret W. Hilgartner1,2,3,4,5, S.T. Cox1,2,3,4,5, Ann-Margeret Little1,2,3,4,5, Graeme Alexander1,2,3,4,5, Matthew Cramp1,2,3,4,5, Stephen J. O’Brien1,2,3,4,5, William Rosenberg1,2,3,4,5, David L. Thomas1,2,3,4,5, Mary Carrington1,3,4,5
1Basic Research Program, Scientific Applications International Corporation Frederick, Inc., Laboratory of Genomic Diversity, NCI Frederick, Frederick, MD 21702, USA.
2Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
3Liver Group, Division of Infection, Inflammation, and Repair, Southampton University, Southampton 5016 6YD, UK.
4New York Academy of Medicine, New York, NY 10029, USA.
5Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.

Tóm tắt

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.

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We would like to acknowledge the many individuals who assisted in collecting samples the research participants health care providers and P. Karacki and J.-H. Lee for technical assistance. This publication has been funded in part with funds from the National Cancer Institute National Institutes of Health under contracts NO1-CO-12400 N01-CP-33002 and N01-CP-01004; NIH grants DA00441 DA04334 and DA13324; the Bureau of Maternal and Child Health and Resources Development (MCJ-060570); the National Institute of Child Health and Human Development (NO1-HD-4-3200); the Centers for Disease Control and Prevention; the National Institute of Mental Health; the Medical Research Council (UK); Hope Charity; and the National Health Service (UK) research and development program. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services nor does mention of trade names commercial products or organizations imply endorsement by the U.S. government.

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American Association for the Advancement of Science (AAAS)

Tập 305 Số 5685

872-874

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