scholarly journals miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Marzena Lenart ◽  
Edyta Działo ◽  
Anna Kluczewska ◽  
Kazimierz Węglarczyk ◽  
Anna Szaflarska ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Expression Pattern ◽  
Mirna Expression ◽  
Nk Cell ◽  
Antiviral Response ◽  
Cell Development ◽  
Mirna Expression Pattern ◽  
Simplex Virus

Severe and/or recurrent infection with Herpes simplex virus (HSV) is observed in a large group of patients treated in clinical immunology facilities. Atypical and prolonged HSV infection is the most common clinical manifestation of disturbed NK cell development and functions, yet the molecular basis of these disorders is still largely unknown. Since recent findings indicated the importance of miRNA in regulating NK cell development, maturation and functions, the aim of our study was to investigate miRNA expression pattern in NK cells in patients with severe and/or recurrent infections with HSV and analyze the role of these miRNAs in NK cell antiviral response. As a result, miRNA expression pattern analysis of human best known 754 miRNAs revealed that patients with severe and/or recurrent HSV infection had substantially upregulated expression of four miRNAs: miR-27b, miR-199b, miR-369-3p and miR-491-3p, when compared to healthy controls. Selective inhibition of miR-27b, miR-199b, miR-369-3p and miR-491-3p expression in NK-92 cells resulted in profound upregulation of 4 genes (APOBEC3G, MAP2K3, MAVS and TLR7) and downregulation of 36 genes taking part in antiviral response or associated with signaling pathways of Toll-like receptors (TLR), NOD-like receptors, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and type I IFN-related response. Additionally, flow cytometry analysis revealed that miR-369-3p and miR-491-3p inhibitors downregulated NK cell intracellular perforin expression, while the expression of granzyme B and IFNγ remained unchanged. Taken together, our study suggests a novel mechanism which may promote recurrence and severity of HSV infection, based on miRNAs-dependent posttranscriptional regulation of genes taking part in antiviral response of human NK cells.

scholarly journals Natural Killer Cells as Novel Helpers in Anti-Herpes Simplex Virus Immune Response

2008 ◽  
Vol 82 (21) ◽  
pp. 10820-10831 ◽  
Author(s):  
Subhadra Nandakumar ◽  
Stacie N. Woolard ◽  
Dorothy Yuan ◽  
Barry T. Rouse ◽  
Uday Kumaraguru
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Nk Cell ◽  
Adaptive Immune Response ◽  
T Cell Response ◽  
Simplex Virus

ABSTRACT Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8+ cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8+ T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.

scholarly journals Dendritic Cells Are Required for Optimal Activation of Natural Killer Functions following Primary Infection with Herpes Simplex Virus Type 1

2009 ◽  
Vol 83 (7) ◽  
pp. 3175-3186 ◽  
Author(s):  
Sadik H. Kassim ◽  
Naveen K. Rajasagi ◽  
Barry W. Ritz ◽  
Stephen B. Pruett ◽  
Elizabeth M. Gardner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Nk Cell ◽  
Ifn Γ ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Natural killer (NK) cells play an important role in the optimal clearance of herpes simplex virus type 1 (HSV-1) infection in mice. Activated NK cells function via cytokine secretion or direct cytolysis of target cells; dendritic cells (DCs) are thought to make critical contributions in the activation of both of these functions. Yet, the magnitude and physiological relevance of DC-mediated NK cell activation in vivo is not completely understood. To examine the contribution of DC help in regulating NK cell functions after infection with HSV-1, we utilized a transgenic mouse model that allows the transient ablation of DCs. Using this approach, it was found that the gamma interferon (IFN-γ) expression potential of NK cells is quantitatively and qualitatively impaired in the absence of DCs. With regard to priming of NK cytolytic functions, the ablation of DCs did not significantly affect cytotoxic protein expression by NK cells. An in vivo cytolytic assay did, however, reveal impairments in the magnitude of NK cell cytotoxicity. Overall, this study provides direct evidence that functional DCs are required for optimal IFN-γ expression and cytolytic function by NK cells following infection with HSV-1.

scholarly journals ICP0 Prevents RNase L-Independent rRNA Cleavage in Herpes Simplex Virus Type 1-Infected Cells

2006 ◽  
Vol 80 (1) ◽  
pp. 218-225 ◽  
Author(s):  
Paul T. Sobol ◽  
Karen L. Mossman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infection ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Antiviral Response ◽  
Rnase L ◽  
Simplex Virus ◽  
Rrna Degradation

ABSTRACT The classical interferon (IFN)-dependent antiviral response to viral infection involves the regulation of IFN-stimulated genes (ISGs), one being the gene encoding cellular endoribonuclease RNase L, which arrests protein synthesis and induces apoptosis by nonspecifically cleaving rRNA. Recently, the herpes simplex virus type 1 (HSV-1) protein ICP0 has been shown to block the induction of ISGs by subverting the IFN pathway upstream of the 2′-5′-oligoadenylate synthetase (OAS)/RNase L pathway. We report that ICP0 also prevents rRNA degradation at late stages of HSV-1 infection, independent of its E3 ubiquitin ligase activity, and that the resultant rRNA degradation is independent of the classical RNase L antiviral pathway. Moreover, the degradation is independent of the viral RNase vhs and is independent of IFN response factor 3. These studies indicate the existence of another, previously unidentified, RNase that is part of the host antiviral response to viral infection.

In VitroCytotoxic Activity of Cord Blood NK Cells against Herpes Simplex Virus Type-1 Infected Purified Human Term Villous Cytotrophoblast

1994 ◽  
Vol 7 (3) ◽  
pp. 133-140 ◽  
Author(s):  
MILAN ZDRAVKOVIC ◽  
GEORGE ABOAGYE-MATHIESEN ◽  
VLADIMIR ZACHAR ◽  
PETER MOSBORG-PETERSEN ◽  
FERENC D. TÓTH ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cord Blood ◽  
Nk Cells ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus

scholarly journals An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Xu ◽  
Lei Tian ◽  
Jing Chen ◽  
Jing Wang ◽  
Rui Ma ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Herpes Virus ◽  
Innate Immune ◽  
Full Length ◽  
Herpes Simplex Virus 1 ◽  
Oncolytic Herpes Simplex Virus ◽  
Herpès Virus ◽  
Simplex Virus

AbstractOncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 ‘don’t eat me’ signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.

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