KIR2DL3+NKG2A− natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs

Thoens, Christine; Berger, Christoph T.; Trippler, Martin; Siemann, Holger; Lutterbeck, M; Broering, Ruth; Schlaak, J. F.; Heinemann, Falko M.; Heinold, Andreas; Nattermann, Jacob; Scherbaum, Norbert; Alter, Galit; Timm, Joerg

doi:10.1016/j.jhep.2014.04.020

Cited by 39 publications

(42 citation statements)

References 30 publications

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“…NKG2A low NK cells have also been implicated in HCV protection and control29. Furthermore, higher levels of NKG2A expression on NK cells were demonstrable in HCV-infected patients who failed to achieve a sustained virologic response during Peg-IFN and ribavirin therapy3031.…”

Section: Discussionmentioning

confidence: 99%

NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

Shen

Liu

et al. 2016

Sci Rep

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A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30+ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. The responders and non-responders differed in the frequency of polyfunctional IFN-γ+ CD107+ NK cells. In addition, the increase in NKp30+ NK cells was negatively correlated with the HBV viral load and plasma HBeAg. Moreover, it was found that IL-15 may contribute to the up-regulation of NKp30 on the NK cells, and this up-regulation was not induced in vitro by Peg-IFN-α-2b alone. However, in the non-responders, these NKp30+ NK cells were dysfunctional because of increased NKG2A expression, which partly explains the inactivation of NKp30+ NK cells and the reduced capacity of these cells to produce antiviral cytokines. These findings may provide a new mechanism to explain the variable efficacy of Peg-IFN-α-2b therapy.

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Section: Discussionmentioning

confidence: 99%

NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

Shen

Liu

et al. 2016

Sci Rep

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“…Expression or absence of particular receptors on NK cells was found to influence the course of HCV infection. For example, KIR2DL3 + NKG2A À NK cells were shown to be associated with protection from HCV infection in drug users [25].…”

Section: Discussionmentioning

confidence: 99%

Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia

et al. 2015

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“…In a study of 1,037 patients, spontaneous HCV clearance was associated with the presence of KIR2DLR3 with homozygocity for the HLA-C1 ligand [52]. Although the association of spontaneous HCV clearance with KIR2DLR3 and HLA-C1 homozygocity was [53] or tended to be [54] [ [55][56][57]. Reversely, carriage of KIR2DS3 together HLA-C2 was consistently associated with failure to clear HCV, either spontaneously [54] or after treatment in a cohort of HIV-1/HCV co-infected patients [58].…”

Section: Genetic Associations With Spontaneous and Treatment-induced mentioning

confidence: 99%

Host – hepatitis C viral interactions: The role of genetics

Heim

Bochud

George

2016

Journal of Hepatology

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Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions.

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KIR2DL3+NKG2A− natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs

Cited by 39 publications

References 30 publications

NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

NKp30+ NK cells are associated with HBV control during pegylated-interferon-alpha-2b therapy of chronic hepatitis B

Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia

Host – hepatitis C viral interactions: The role of genetics

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