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

Author:

Khakoo Salim I.12345,Thio Chloe L.12345,Martin Maureen P.12345,Brooks Collin R.12345,Gao Xiaojiang12345,Astemborski Jacquie12345,Cheng Jie12345,Goedert James J.12345,Vlahov David12345,Hilgartner Margaret12345,Cox Steven12345,Little Ann-Margeret12345,Alexander Graeme J.12345,Cramp Matthew E.12345,O'Brien Stephen J.12345,Rosenberg William M. C.12345,Thomas David L.12345,Carrington Mary12345

Affiliation:

1. Liver Group, Division of Infection, Inflammation, and Repair, Southampton University, Southampton 5016 6YD, UK.

2. Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.

3. Basic Research Program, Scientific Applications International Corporation Frederick, Inc., Laboratory of Genomic Diversity, NCI Frederick, Frederick, MD 21702, USA.

4. Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.

5. New York Academy of Medicine, New York, NY 10029, USA.

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 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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