Natural killer cells during primary varicella zoster virus infection

Malavige, Gathsaurie Neelika; Jones, Louise; Kamaladasa, S. D.; Wijewickrama, Ananda; Seneviratne, Suranjith L.; Black, Antony P.; Ogg, Graham S.

doi:10.1016/j.jinf.2010.05.004

Cited by 4 publications

(2 citation statements)

References 16 publications

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“…NK cells are an essential component of the early host response to infection, and have been implicated in responding to VZV infection during both varicella and herpes zoster [ 60 – 63 ]. Considering this, it is surprising that characterisation of how VZV interacts with NK cells has mostly not been pursued.…”

Section: Discussionmentioning

confidence: 99%

Varicella zoster virus productively infects human natural killer cells and manipulates phenotype

et al. 2018

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Varicella zoster virus (VZV) is a ubiquitous human alphaherpesvirus, responsible for varicella upon primary infection and herpes zoster following reactivation from latency. To establish lifelong infection, VZV employs strategies to evade and manipulate the immune system to its advantage in disseminating virus. As innate lymphocytes, natural killer (NK) cells are part of the early immune response to infection, and have been implicated in controlling VZV infection in patients. Understanding of how VZV directly interacts with NK cells, however, has not been investigated in detail. In this study, we provide the first evidence that VZV is capable of infecting human NK cells from peripheral blood in vitro. VZV infection of NK cells is productive, supporting the full kinetic cascade of viral gene expression and producing new infectious virus which was transmitted to epithelial cells in culture. We determined by flow cytometry that NK cell infection with VZV was not only preferential for the mature CD56dim NK cell subset, but also drove acquisition of the terminally-differentiated maturity marker CD57. Interpretation of high dimensional flow cytometry data with tSNE analysis revealed that culture of NK cells with VZV also induced a potent loss of expression of the low-affinity IgG Fc receptor CD16 on the cell surface. Notably, VZV infection of NK cells upregulated surface expression of chemokine receptors associated with trafficking to the skin –a crucial site in VZV disease where highly infectious lesions develop. We demonstrate that VZV actively manipulates the NK cell phenotype through productive infection, and propose a potential role for NK cells in VZV pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Varicella zoster virus productively infects human natural killer cells and manipulates phenotype

et al. 2018

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“…There is accumulating evidence that NK cells are critically involved in the control of infection by many viruses, 2,[29][30][31][32] and immunogenetic analyses indicate that NK cells may influence the outcome of HCV infection. 2 Moreover, in vitro studies suggest that NK cells should also be able to recognize and kill HCVinfected hepatocytes in vivo.…”

Section: Discussionmentioning

confidence: 99%

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

et al. 2012

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Natural killer (NK) cells play a role in the early control and natural course of hepatitis C virus (HCV) infection. NK cell function is regulated by a multitude of receptors, including activating NKp46 receptor. However, reports on NKp46 in hepatitis C are controversial. Therefore, we investigated the hepatic recruitment and function of NKp46(1) NK cells, considering differential surface expression of NKp46 resulting in NKp46 High and NKp46 Dim subsets. Intra-and extrahepatic NK-cell subsets from HCV-infected patients were characterized by flow cytometry. Cytotoxic activity and interferon-gamma (IFN-c) secretion were studied using K-562, P815, and primary hepatic stellate cells as targets. Anti-HCV activity of NK-cell subsets was studied using the replicon system. Density of NKp46 surface expression clearly segregated NKp46 Dim and NKp46 High subsets, which differed significantly with respect to the coexpression of maturation markers and NK-cell receptors. More important, NKp46 High NK cells showed a higher cytolytic activity and stronger IFN-c secretion than NKp46 Dim NK cells. Accordingly, NKp46 High NK cells efficiently blocked HCV replication in vitro. Blocking experiments confirmed an important role for the NKp46 receptor. Furthermore, we found an intrahepatic accumulation of NKp46 High NK cells. Of note, high cytolytic activity of NKp46 High NK cells was also confirmed in the intrahepatic NK-cell population, and the frequency of intrahepatic NKp46 High NK cells was inversely correlated with HCV-RNA levels and fibrosis stage. Conclusions: NKp46 High expression defines a specific NK-cell subset that may be involved in both the suppression of HCV replication and HCV-associated liver damage underpinning the role of NK cells in the immunopathogenesis of HCV. (HEPATOLOGY 2012;56:1201-1213 See Editorial on Page 1197 I nfection with the hepatitis C virus (HCV) often results in chronic liver disease. Elimination of HCV infection requires the coordinated function of the innate and the adaptive immune system. Natural killer (NK) cells constitute a major component of the intrahepatic lymphocyte pool. In contrast to the peripheral blood, which contains approximately 5%-10% NK cells, intrahepatic lymphocytes comprise approximately 30% NK cells, and the percentage of intrahepatic NK cells may increase >50% in liver diseases. 1 Immunogenetic analyses indicate that NK cells may influence the outcome of acute HCV infection as well as immunopathogenesis in chronic hepatitis C (CHC). 2 Accordingly, in vitro studies suggest that NK cells are able to recognize and kill HCV-infected hepatocytes in vivo. 3 However, published data on phenotype and function of NK cells in HCV infection are controversial. [4][5][6][7][8][9][10][11][12][13]

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NK Cells and their Receptors during Viral Infections

et al. 2011

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Increasing evidence indicates the importance of human natural killer (NK) cells in the immune response against certain viral infections. In the present article, we summarize information on NK cell responses against several viruses and on the nature of NK cell receptor-ligand interactions involved in these responses. Recent studies indicate that NK cells display functional features that are normally attributed exclusively to cells of the adaptive immune system. In this context, experiments both in mice and humans suggest the existence of long-lived NK cells that expand during viral infections and retain a 'memory' of previous exposure to a specific antigen. However, further studies are necessary to better define the characteristics of these long-lived NK cell populations and their role in viral infections.

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Natural killer cells during primary varicella zoster virus infection

Cited by 4 publications

References 16 publications

Varicella zoster virus productively infects human natural killer cells and manipulates phenotype

Varicella zoster virus productively infects human natural killer cells and manipulates phenotype

Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis

NK Cells and their Receptors during Viral Infections

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