HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.
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.
Liver Group, Division of Infection, Inflammation, and Repair, Southampton University, Southampton 5016 6YD, UK. sik@soton.ac.uk
Salim I
SI
Khakoo
Chloe L
CL
Thio
Maureen P
MP
Martin
Collin R
CR
Brooks
Xiaojiang
X
Gao
Jacquie
J
Astemborski
Jie
J
Cheng
James J
JJ
Goedert
David
D
Vlahov
Margaret
M
Hilgartner
Steven
S
Cox
Ann-Margeret
AM
Little
Graeme J
GJ
Alexander
Matthew E
ME
Cramp
Stephen J
SJ
O'Brien
William M C
WM
Rosenberg
David L
DL
Thomas
Mary
M
Carrington
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000483:Alleles; D001803:Blood Transfusion; D002648:Child; D015331:Cohort Studies; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology* / Q000635:transmission / Q000821:virology; D006720:Homozygote; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008297:Male; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3; D012044:Regression Analysis; D044465:White People / Q000235:genetics
D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054344:Receptors, KIR2DL3