Relevance of HLA-KIR Genes in Chronic Hepatitis C Virus Infection [617919]

Relevance of HLA-KIR Genes in Chronic Hepatitis C Virus Infection
Outcome
Ileana Constantinescu1,2*, Larisa Denisa Ursu2
1Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
2Centre for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania
*Corresponding author : Ileana Constantinescu, Department for Immunogenetics and Virology, Fundeni Clinical Institute, Carol Davila Un iversity of Medicine and
Pharmacy, Bucharest, Romania
Received date: July 02, 2018; Accepted date: July 06, 2018; Published date: July 11, 2018
Copyright: ©2018 Constantinescu I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Editorial
Hepatitis C V irus (HCV) is responsible for over 170 million
chronically infected worldwide people, most patients develop a lifetime
chronic infection that can lead to severe liver pathology [1].
Substantial research evidences suggest that the innate immune
response significantly contributes to HCV outcome [2,3]. Natural
Killer (NK) cells have efficient anti-viral functions including direct
cytotoxicity of infected cells and production of inflammatory cytokines
[4]. Killer cell immunoglobulin-like receptors (KIRs) play a major role
in regulating the activity of NK cells involved against viral infections,
autoimmune diseases, cancers or post-transplantation [5-7].
Many recent studies have reviewed the importance of NK cells in
chronic HCV infection outcome and the interactions between the KIR
and HLA genes. Both molecules have structural polymorphisms which
could be referred to a particular clinical condition [5-11].
Interaction between KIR and HLA-C molecules is the dominant
control mechanism of the host NK cells. Genetic studies reveal that, in
the early phase of HCV infection, specific KIR and HLA-C pairs are
associated with the spontaneous resolution of HCV infection [8,9].
KIR2DL1 receptors recognize HLA-C group 2 antigens (lysine in
position 80), KIR2DL2/3 receptors recognizes HLA-C group 1 antigens
(asparagine in position 80) and KIR3DL1 is the receptor for HLA Bw4
molecules [10,11].
KIR2DL3-mediated inhibition of NK cells protects from HCV
persistence, since KIR2DL3 has a lower affinity for its HLA-C ligand
than other KIRs [12]. KIR2DL3 binds HLA-C1 with a weaker affinity
compared with KIR2DL2 binding of HLA-C1. NK cells in HCV
carriers with this combination of receptors and ligands could be more
easily activated during HCV infection resulting in a better outcome
[8,11].
Activatory KIR2DS3 gene interaction with HLA-C2 is significantly
increased in HCV patients having a role in the development of chronic
viral infection [12]. The authors of this study identify a strong
influence of KIR B haplotype (and HLA-C2) for the activation of NK
cells. In other previous study, a beneficial effect of a KIR A haplotype
(with HLA-C1 ) was observed [8,13].
The role of KIR genes in susceptibility to chronic HCV infection and
viral load level variations were revealed in different KIR2DS3-
KIR2DS5 genotypes combinations.
Kusnierczyk et al. have found that in patients with KIR2DS3+/
KIR2DS5- the HCV viremia levels was 2.6 times lower than in patients
with other KIR genotypes [14]. In contrast, a study conducted byPodhorzer et al. has shown that KIR2DS3 expression was correlated
with high viral load levels [15].
Our unpublished data, show on HCV Romanian infected patients,
that in KIR2DS3+/KIR2DS5- genotype HCV viremia mean values
were 2.2 times lower than in other genotypes.
All these evidence-based results underline that the immune
response against HCV is complex. Interactions between NK activatory-
inhibitory KIR genes and HLA alleles are important and challenging.
These insights could offer more information related to different
outcomes in HCV chronically infected individuals. Variable
interactions between KIRs and HLA class I and class II molecules have
a relevant influence on immunopathogenesis of HCV and have a
significant impact on NK cells function.
Understanding HCV immunopathogenesis for an improved clinical
management of chronic hepatitis C is further required.
References
1. World Health Organization (2017) New hepatitis data highlight need for
urgent global response. WHO.
2. Horner SM, Gale M Jr (2013) Regulation of hepatic innate immunity by
hepatitis C virus. Nature Med 19: 879-888.
3. Bowen DG, Walker CM (2005) Adaptive immune responses in acute and
chronic hepatitis C virus infection. Nature 436: 946-952.
4. Fallahi P , Ferri C, Ferrari SM, Corrado A, Sansonno D, et al. (2012)
Cytokines and HCV-related disorders. Clin Developmental Immunol 2012:
468107.
5. Gardiner CM (2015) NK cell function and receptor diversity in the context
of HCV infection. Front Microbiol 6: 1061.
6. Moretta L, Moretta A (2004) Killer immunoglobulin-like receptors. Curr
Opin Immunol 16: 626-633.
7. Constantinescu I, Nedelcu FD, Toader MA, Vasile D, Zaharia M (2006)
Evaluation of KIR genotypes and cytokine gene polymorphism in
Romanian kidney transplant recipients: Impact on acute and chronic
allograft rejection. Tissue Antigens 67: 505.
8. Khakoo SI, Thio CL, Martin MP , Brooks CR, Gao X (2004) HLA and NK
cell inhibitory receptor genes in resolving hepatitis C virus
infection. Science 305: 872-874.
9. Cheent K, Khakoo SI (2011) Natural killer cells and hepatitis C: action and
reaction. Gut 60: 268-278.
10. V ivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, et al. (2011)
Innate or adaptive immunity? The example of natural killer cells. Science
331: 44-49.
11. Guethlein LA, Norman PJ, Hilton HG, Parham P (2015) Co-evolution of
MHC class I and variable NK cell receptors in placental mammals.
Immunol Rev 267: 259-282.
Immunogenetics: Open AccessImmunogenetics: Open AccessConstantinescu et al., Immunogenet Open Access
2018, 2:1
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12. Romero V , Azocar J, Zuniga J, Clavijo OP , Terreros D, et al. (2008)
Interaction of NK inhibitory receptor genes with HLA-C and MHC class II
alleles in Hepatitis C virus infection outcome. Mol Immunol 45: 2429-2436.
13. Dring MM, Morrison MH, McSharry BP , Guinan KJ, Hagan R, et al.
(2011). Innate immune genes synergize to predict increased risk of chronic
disease in hepatitis C virus infection. Proc Natl Acad Sci USA 108:
5736-5741.
14. Kusnierczyk P , Mozer-Lisewska I, Zwolinska K, Kowala-Piaskowska AE,
Bura MI, et al. (2015) Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus
infection and to viremia. Hum Immunol 76: 102-108.
15. Podhorzer A, Dirchwolf M, Machicote A, Belen S, Montal S, et al. (2017)
The clinical features of patients with chronic hepatitis C virus infections are
associated with killer cell immunoglobulin-like receptor genes and their
expression on the surface of natural killer cells. Front Immunol 8: 1912.
Citation: Constantinescu I and Ursu LD (2018) Relevance of HLA-KIR Genes in Chronic Hepatitis C Virus Infection Outcome . Immunogenet
Open Access 2: e104.
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