Natural killer cell receptor expression in patients with severe and recurrent Herpes simplex virus-1 (HSV-1) infections

Carter, C.; Savic, Sinisa; Cole, June Y.; Wood, Phil

doi:10.1016/j.cellimm.2007.06.002

Cited by 12 publications

(10 citation statements)

References 41 publications

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“…Since PMA and ION act downstream of the surface receptors, this finding suggests that the impaired degranulation in FRH was not caused by defective target cell recognition. This conclusion is supported by a recent study that reported no differences in NK cell receptor expression in FRH patients and healthy controls (9).…”

Section: Discussionsupporting

confidence: 70%

Reduced Degranulation of NK Cells in Patients with Frequently Recurring Herpes

Муругин

Зуйкова

Murugina

et al. 2011

Clin. Vaccine Immunol.

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NK cells lyse virus-infected cells by degranulation; however, alterations in NK cell degranulation in persistent viral infections have not been directly studied. Earlier reports have documented a decrease in NK activity in patients with frequently recurring herpes (FRH). We corroborate these findings by showing that the degranulation responses of blood NK cells from patients with FRH, both during relapse and during remission, are significantly lower than those in healthy donors. The impaired degranulation was probably not caused by defective target cell recognition, since it was observed upon stimulation both with K562 cells and with a receptor-independent stimulus (phorbol 12-myristate 13-acetate plus ionomycin). We also show that the intracellular expression of perforin and CD107a by NK cells from patients with FRH is not different from that in healthy donors, thus excluding that the low NK cell degranulation in FRH is caused by a smaller size of the lytic granule compartment. We confirm previous reports on lowered NK activity in FRH patients and show that NK activity is significantly impaired only during remission, but not relapse; the causes for the discrepancy between the low degranulation and "normal" NK cell activity during relapse are discussed. In all, these data point at the deficit of NK cell degranulation in FRH. Whether this is a predisposing factor or a consequence of herpes simplex virus infection requires further investigation.

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Section: Discussionsupporting

confidence: 70%

Reduced Degranulation of NK Cells in Patients with Frequently Recurring Herpes

Муругин

Зуйкова

Murugina

et al. 2011

Clin. Vaccine Immunol.

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“…Recurrent HSV infections in the skin and mucosae appear to be controlled mainly by the host cellular immune response, such as T lymphocytes, macrophages, natural killer cells, and, as demonstrated recently, type I interferon (IFN)-producing plasmacytoid dendritic cells (10,13,15,22,29,45,47). High levels of preexisting neutralizing antibodies may play a role in preventing HSV spread and viremia.…”

mentioning

confidence: 97%

Impact of Valency of a Glycoprotein B-Specific Monoclonal Antibody on Neutralization of Herpes Simplex Virus

Krawczyk

Krauß

Eis‐Hübinger³

et al. 2011

J Virol

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Herpes simplex virus (HSV) glycoprotein B (gB) is an integral part of the multicomponent fusion system required for virus entry and cell-cell fusion. Here we investigated the mechanism of viral neutralization by the monoclonal antibody (MAb) 2c, which specifically recognizes the gB of HSV type 1 (HSV-1) and HSV-2. Binding of MAb 2c to a type-common discontinuous epitope of gB resulted in highly efficient neutralization of HSV at the postbinding/prefusion stage and completely abrogated the viral cell-to-cell spread in vitro. Mapping of the antigenic site recognized by MAb 2c to the recently solved crystal structure of the HSV-1 gB ectodomain revealed that its discontinuous epitope is only partially accessible within the observed multidomain trimer conformation of gB, likely representing its postfusion conformation. To investigate how MAb 2c may interact with gB during membrane fusion, we characterized the properties of monovalent (Fab and scFv) and bivalent [IgG and F(ab) 2 ] derivatives of MAb 2c. Our data show that the neutralization capacity of MAb 2c is dependent on cross-linkage of gB trimers. As a result, only bivalent derivatives of MAb 2c exhibited high neutralizing activity in vitro. Notably, bivalent MAb 2c not only was capable of preventing mucocutaneous disease in severely immunodeficient NOD/SCID mice upon vaginal HSV-1 challenge but also protected animals even with neuronal HSV infection. We also report for the first time that an anti-gB specific monoclonal antibody prevents HSV-1-induced encephalitis entirely independently from complement activation, antibodydependent cellular cytotoxicity, and cellular immunity. This indicates the potential for further development of MAb 2c as an anti-HSV drug.Herpes simplex virus (HSV) is a neuroinvasive human pathogen that critically depends on efficient infection of distinct target cells within a host. At the time of primary lytic infection, HSV replicates in peripheral mucocutaneous tissues and releases virions. A decisive characteristic of HSV infections in animals and humans is the establishment of a lifelong latency. HSV spreads from infected epithelial cells to axons of sensory neurons innervating the site of the primary infection, followed by retrograde transport to the respective dorsal root ganglia (12). Recurrent infections result from reactivation in neuronal cells, followed by virus replication and anterograde transport to cells at peripheral sites innervated by the respective neurons. Transmission between cells without diffusion through the extracellular environment represents a major route for HSV to spread between tissues and is thus a very efficient way for circumventing immunological barriers of the humoral immune response. Regardless of the dissemination pathway, however, fusion of the viral envelope with host membranes for delivery of the viral genome across the cellular lipid bilayer is essential for viral replication. In contrast to that of most other enveloped viruses, entry of herpesviruses into mammalian cells requires a multicomponent sy...

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“…In particular we examined the expression of important natural killer cytotoxicity receptors NKp30 and NKp46 as well as NKG2D according to previously reported methods. 6 Patients received lenalidomide 25mg/d in combination with a starting dose of 480mg/cycle (high dose) or 160mg/cycle (low dose) dexamethasone, the dose of dexamethasone being tapered after cycle 6. The absolute NK cell number nonsignificantly decreased over the 10 cycles analyzed (baseline 346 Ϯ 76 cells/L vs 196 Ϯ 26 cells/L at cycle 10; P ϭ NS) although the relative frequency (variation from baseline) increased.…”

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confidence: 99%