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

  title={HLA and NK Cell Inhibitory Receptor Genes in Resolving Hepatitis C Virus Infection},
  author={Salim I. Khakoo and Chloe L. Thio and Maureen P. Martin and Collin R. Brooks and Xiaojiang Gao and Jacquie Astemborski and Jie Cheng and James J. Goedert and David Vlahov and Margaret W. Hilgartner and Steven T Cox and Ann-Margaret Little and Graeme J Alexander and Matthew E. Cramp and Stephen J. O’Brien and William M. Rosenberg and David L. Thomas and Mary N. Carrington},
  pages={872 - 874}
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… 
Hepatitis C virus and the threshold of natural killer cell inhibition
The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.
Influence of inhibitory killer immunoglobulin-like receptors and their HLA-C ligands on resolving hepatitis C virus infection.
This workshop component addressed the influence of KIR genotypes and their HLA ligands on resolving HCV infection and the implications of the results of the study of Lopez-Vazquez et al. on KIR and HCV disease progression.
Natural Killer Cell Function and Dysfunction in Hepatitis C Virus Infection
Direct in vivo and in vitro evidence of compromised NK function in chronic HCV infection in conjunction with significant epidemiological associations between the outcome ofHCV infection and certain combinations of NK cell regulatory receptor and class I human histocompatibility linked antigen (HLA) genotypes indicate that NK cells are important in the immune response against HCV infections.
Are KIR-HLA Polymorphisms Relevant for the Outcome of Chronic Infected Hepatitis C Virus Patients?
Improving understanding of NK cells could help to gain further insight into the virus-host interaction and the mechanisms of viral persistence, and there is a great potential for the use of KIR genes as a prognostic tool for the development of complications such as liver cirrhosis and HCC.
Decreased interferon‐γ production by NK cells from KIR haplotype B carriers in hepatitis C virus infection
  • D. Mele, A. Pasi, S. Varchetta
  • Biology, Medicine
    Liver international : official journal of the International Association for the Study of the Liver
  • 2019
This work analysed whether its expression may affect natural killer (NK) cell function in the presence or absence of its principal ligand HLA‐Bw4 in KIR haplotype A and B carriers, which are characterized by a different representation of activating and inhibitory KIRs.
Interactions Between KIR3DS1 and HLA-F Activate Natural Killer Cells to Control HCV Replication in Cell Culture.
It is found that the KIR3DS1 ligand HLA-F is up-regulated on HCV-infected cells, and that interactions between KIR2DS1 and HLAF contribute to NK cell-mediated control of HCV.
KIR2DL2 Enhances Protective and Detrimental HLA Class I-Mediated Immunity in Chronic Viral Infection
It is concluded that inhibitory KIRs, in synergy with T cells, are a major determinant of the outcome of persistent viral infection.
Epitope and the Killer Cell Immunoglobulin-Like Receptor 3 DS 1 Gene against the Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Infection
It was found that the human leukocyte antigen–Bw4I80 epitope and the KIR3DS1 gene were more frequent in HCV carriers than in patients with hepatocellular carcinoma.


Inhibition of Natural Killer Cells through Engagement of CD81 by the Major Hepatitis C Virus Envelope Protein
It is reported that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells, implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities ofNK cells and allowing the virus to establish itself as a chronic infection.
Direct Recognition of Cytomegalovirus by Activating and Inhibitory NK Cell Receptors
Mouse cytomegalovirus encodes an MHC-like protein that binds to an inhibitory NK cell receptor in certain MCMV-susceptible mice, and this viral protein engages a related activating receptor and confers host protection.
Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS
The strongest synergistic effect of these loci was on progression to depletion of CD4+ T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.
HLA-Cw*04 and Hepatitis C Virus Persistence
The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy) and these cells may be involved in recovery from HCV infection.
Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.
An activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses is defined.
DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection
The data suggest a biphasic mechanism of viral clearance dependent on both the innate and adaptive immune responses and provide insight into the response of the liver to a hepatotropic viral infection.
Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition.
Results show that KIR2DL receptors are specific for HLA-C, but that recognition of H LA-C allotypes appears more permissive than indicated by previous functional experiments.