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

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...

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Autores principales: Lenart, Marzena, Działo, Edyta, Kluczewska, Anna, Węglarczyk, Kazimierz, Szaflarska, Anna, Rutkowska-Zapała, Magdalena, Surmiak, Marcin, Sanak, Marek, Pituch-Noworolska, Anna, Siedlar, Maciej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931645/
https://www.ncbi.nlm.nih.gov/pubmed/33679688
http://dx.doi.org/10.3389/fimmu.2020.589866
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author Lenart, Marzena
Działo, Edyta
Kluczewska, Anna
Węglarczyk, Kazimierz
Szaflarska, Anna
Rutkowska-Zapała, Magdalena
Surmiak, Marcin
Sanak, Marek
Pituch-Noworolska, Anna
Siedlar, Maciej
author_facet Lenart, Marzena
Działo, Edyta
Kluczewska, Anna
Węglarczyk, Kazimierz
Szaflarska, Anna
Rutkowska-Zapała, Magdalena
Surmiak, Marcin
Sanak, Marek
Pituch-Noworolska, Anna
Siedlar, Maciej
author_sort Lenart, Marzena
collection PubMed
description 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.
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spelling pubmed-79316452021-03-05 miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections Lenart, Marzena Działo, Edyta Kluczewska, Anna Węglarczyk, Kazimierz Szaflarska, Anna Rutkowska-Zapała, Magdalena Surmiak, Marcin Sanak, Marek Pituch-Noworolska, Anna Siedlar, Maciej Front Immunol Immunology 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. Frontiers Media S.A. 2021-01-25 /pmc/articles/PMC7931645/ /pubmed/33679688 http://dx.doi.org/10.3389/fimmu.2020.589866 Text en Copyright © 2021 Lenart, Działo, Kluczewska, Węglarczyk, Szaflarska, Rutkowska-Zapała, Surmiak, Sanak, Pituch-Noworolska and Siedlar http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Lenart, Marzena
Działo, Edyta
Kluczewska, Anna
Węglarczyk, Kazimierz
Szaflarska, Anna
Rutkowska-Zapała, Magdalena
Surmiak, Marcin
Sanak, Marek
Pituch-Noworolska, Anna
Siedlar, Maciej
miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections
title miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections
title_full miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections
title_fullStr miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections
title_full_unstemmed miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections
title_short miRNA Regulation of NK Cells Antiviral Response in Children With Severe and/or Recurrent Herpes Simplex Virus Infections
title_sort mirna regulation of nk cells antiviral response in children with severe and/or recurrent herpes simplex virus infections
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931645/
https://www.ncbi.nlm.nih.gov/pubmed/33679688
http://dx.doi.org/10.3389/fimmu.2020.589866
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