Protective KIR-HLA Interactions for HCV Infection in Intravenous Drug Users

Overview

Journal Mol Immunol

Specialties Allergy & Immunology
Molecular Biology

Date 2009 Jun 26

PMID 19552960

Citations 10

Authors

Joaquin Zuniga

Viviana Romero

Jose Azocar

Daniel Terreros

Maria Ines Vargas-Rojas

Diana Torres-Garcia

Luis Jimenez-Alvarez

Gilberto Vargas-Alarcon

Julio Granados-Montiel

Zaheed Husain

Raymond T Chung

Chester A Alper

Edmond J Yunis

Affiliations

Soon will be listed here.

Abstract

Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC=0.01, OR=0.07; KIR2DL2 and/or KIR2DL3+KIR2DS4, pC=0.01, OR=0.39) and HLA-C1 homozygous genotypes (HLA-C1+KIR2DS4, pC=0.02, OR=0.43; HLA-C1+KIR2DL2+KIR2DS4, pC=0.02, OR=0.40) together with the activating receptor KIR2DS4 (HLA-C1+KIR2DS4+KIR2DL3 and/or KIR2DL2, pC=0.004, OR=0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, plays a determinant role in the regulation of NK cell antiviral-activity.

Citing Articles

High-resolution phenotyping identifies NK cell subsets that distinguish healthy children from adults.

Mahapatra S, Mace E, Minard C, Forbes L, Vargas-Hernandez A, Duryea T PLoS One. 2017; 12(8):e0181134.

PMID: 28767726 PMC: 5540415. DOI: 10.1371/journal.pone.0181134.

Genetic (KIR, HLA-C) and Some Clinical Parameters Influencing the Level of Liver Enzymes and Early Virologic Response in Patients with Chronic Hepatitis C.

Mozer-Lisewska I, Zwolinska K, Kowala-Piaskowska A, Bura M, Rozplochowski B, Pauli A Arch Immunol Ther Exp (Warsz). 2015; 64(1):65-73.

PMID: 26206121 PMC: 4713718. DOI: 10.1007/s00005-015-0350-1.

Genetic diversity of the KIR/HLA system and susceptibility to hepatitis C virus-related diseases.

De Re V, Caggiari L, De Zorzi M, Repetto O, Zignego A, Izzo F PLoS One. 2015; 10(2):e0117420.

PMID: 25700262 PMC: 4336327. DOI: 10.1371/journal.pone.0117420.

Role of KIR genes and genotypes in susceptibility to or protection against hepatitis B virus infection in a Turkish cohort.

Kibar F, Ozturk O, Ulu A, Erken E, Inal S, Dinkci S Med Sci Monit. 2014; 20:28-34.

PMID: 24407110 PMC: 3894916. DOI: 10.12659/MSM.889893.

KLRG1 negatively regulates natural killer cell functions through the Akt pathway in individuals with chronic hepatitis C virus infection.

Wang J, Cheng Y, Shi L, Ying R, Wu X, Li G J Virol. 2013; 87(21):11626-36.

PMID: 23966413 PMC: 3807337. DOI: 10.1128/JVI.01515-13.

References

Goncalves R, Jesus J, Fernandes A, Brehm A . Genetic profile of a multi-ethnic population from Guiné-Bissau (west African coast) using the new PowerPlex 16 System kit. Forensic Sci Int. 2002; 129(1):78-80. DOI: 10.1016/s0379-0738(02)00204-9. View

Khakoo S, Thio C, Martin M, Brooks C, Gao X, Astemborski J . HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science. 2004; 305(5685):872-4. DOI: 10.1126/science.1097670. View

Luszczek W, Manczak M, Cislo M, Nockowski P, Wisniewski A, Jasek M . Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris. Hum Immunol. 2004; 65(7):758-66. DOI: 10.1016/j.humimm.2004.05.008. View

LISKER R, Ramirez E, Briceno R, Granados J, Babinsky V . Gene frequencies and admixture estimates in four Mexican urban centers. Hum Biol. 1990; 62(6):791-801. View

Hsu K, Liu X, Selvakumar A, Mickelson E, OReilly R, Dupont B . Killer Ig-like receptor haplotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J Immunol. 2002; 169(9):5118-29. DOI: 10.4049/jimmunol.169.9.5118. View

Cramp M, Carucci P, Underhill J, Naoumov N, Williams R, Donaldson P . Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia. J Hepatol. 1998; 29(2):207-13. DOI: 10.1016/s0168-8278(98)80005-6. View

Morishima C, Paschal D, Wang C, Yoshihara C, Wood B, Yeo A . Decreased NK cell frequency in chronic hepatitis C does not affect ex vivo cytolytic killing. Hepatology. 2006; 43(3):573-80. DOI: 10.1002/hep.21073. View

Romero V, Azocar J, Zuniga J, Clavijo O, Terreros D, Gu X . Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome. Mol Immunol. 2008; 45(9):2429-36. PMC: 2387047. DOI: 10.1016/j.molimm.2008.01.002. View

Parham P . MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol. 2005; 5(3):201-14. DOI: 10.1038/nri1570. View

10.

Thursz M, Yallop R, Goldin R, Trepo C, Thomas H . Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet. 1999; 354(9196):2119-24. DOI: 10.1016/s0140-6736(99)91443-5. View

11.

Nelson G, Martin M, Gladman D, Wade J, Trowsdale J, Carrington M . Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. J Immunol. 2004; 173(7):4273-6. DOI: 10.4049/jimmunol.173.7.4273. View

12.

Pritchard J, Rosenberg N . Use of unlinked genetic markers to detect population stratification in association studies. Am J Hum Genet. 1999; 65(1):220-8. PMC: 1378093. DOI: 10.1086/302449. View

13.

Martin M, Gao X, Lee J, Nelson G, Detels R, Goedert J . Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet. 2002; 31(4):429-34. DOI: 10.1038/ng934. View

14.

Husain Z, Levitan E, Larsen C, Mirza N, Younes S, Yunis E . HLA-Cw7 zygosity affects the size of a subset of CD158b+ natural killer cells. J Clin Immunol. 2002; 22(1):28-36. DOI: 10.1023/a:1014204519468. View

15.

van der Slik A, Koeleman B, Verduijn W, Bruining G, Roep B, Giphart M . KIR in type 1 diabetes: disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects. Diabetes. 2003; 52(10):2639-42. DOI: 10.2337/diabetes.52.10.2639. View

16.

Gomez-Lozano N, Vilches C . Genotyping of human killer-cell immunoglobulin-like receptor genes by polymerase chain reaction with sequence-specific primers: an update. Tissue Antigens. 2002; 59(3):184-93. DOI: 10.1034/j.1399-0039.2002.590302.x. View

17.

Katz G, Gazit R, Arnon T, Gonen-Gross T, Tarcic G, Markel G . MHC class I-independent recognition of NK-activating receptor KIR2DS4. J Immunol. 2004; 173(3):1819-25. DOI: 10.4049/jimmunol.173.3.1819. View

18.

Post J, Pan Y, Freeman A, Harvey C, White P, Palladinetti P . Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort. J Infect Dis. 2004; 189(10):1846-55. DOI: 10.1086/383279. View

19.

Husain Z, Alper C, Yunis E, Dubey D . Complex expression of natural killer receptor genes in single natural killer cells. Immunology. 2002; 106(3):373-80. PMC: 1782738. DOI: 10.1046/j.1365-2567.2002.01444.x. View

20.

Zarife M, Reis E, Carmo T, Lopes G, Brandao E, Silva H . Increased frequency of CD56Bright NK-cells, CD3-CD16+CD56- NK-cells and activated CD4+T-cells or B-cells in parallel with CD4+CDC25High T-cells control potentially viremia in blood donors with HCV. J Med Virol. 2008; 81(1):49-59. DOI: 10.1002/jmv.21340. View