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NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells

Herpes simplex virus 1 (HSV-1) can infect a wide range of cell types, including cells of the adaptive and innate immunity but, normally, it completes a fully-permissive replication cycle only in epithelial or neural cells. Complex mechanisms controlling this delicate balance in immune cells and cons...

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Autores principales: Marino-Merlo, Francesca, Papaianni, Emanuela, Frezza, Caterina, Pedatella, Silvana, De Nisco, Mauro, Macchi, Beatrice, Grelli, Sandro, Mastino, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563512/
https://www.ncbi.nlm.nih.gov/pubmed/31083280
http://dx.doi.org/10.3390/v11050428
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author Marino-Merlo, Francesca
Papaianni, Emanuela
Frezza, Caterina
Pedatella, Silvana
De Nisco, Mauro
Macchi, Beatrice
Grelli, Sandro
Mastino, Antonio
author_facet Marino-Merlo, Francesca
Papaianni, Emanuela
Frezza, Caterina
Pedatella, Silvana
De Nisco, Mauro
Macchi, Beatrice
Grelli, Sandro
Mastino, Antonio
author_sort Marino-Merlo, Francesca
collection PubMed
description Herpes simplex virus 1 (HSV-1) can infect a wide range of cell types, including cells of the adaptive and innate immunity but, normally, it completes a fully-permissive replication cycle only in epithelial or neural cells. Complex mechanisms controlling this delicate balance in immune cells and consequent restriction of HSV-1 infection in these cells have not been completely elucidated. We have recently demonstrated that the transcription factor nuclear factor kappa B (NF-κB) can act as a main permissiveness regulator of HSV-1 infection in monocytic cells, however, mediators involved in this regulation have not been identified. To better define mechanisms involved in this phenomenon and, particularly, the possible involvement of ROS, wild type U937 cells or U937 cells stably transfected with a dominant-negative (DN) IκB-mutant and selenium-containing compounds, as anti-oxidants, were utilized. The main results can be summarized as follows. HSV-1 infection induces an immediate ROS production in U937 monocytic cells that can efficiently activate NF-κB but not in DN-IκB-mutant cells. Treatment with selenium-containing antioxidants efficiently inhibited HSV-1-induced ROS generation while producing increased levels of HSV-1 replication and a reduction of HSV-1-induced NF-κB activation in U937 monocytic cells. Our results suggest a scenario in which an efficient NF-κB-dependent ROS production in response to infection could contribute in limiting HSV-1 replication in monocytes/macrophages, thus avoiding possible irreparable damage to the innate immune system of the host during HSV-1 infection.
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spelling pubmed-65635122019-06-17 NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells Marino-Merlo, Francesca Papaianni, Emanuela Frezza, Caterina Pedatella, Silvana De Nisco, Mauro Macchi, Beatrice Grelli, Sandro Mastino, Antonio Viruses Article Herpes simplex virus 1 (HSV-1) can infect a wide range of cell types, including cells of the adaptive and innate immunity but, normally, it completes a fully-permissive replication cycle only in epithelial or neural cells. Complex mechanisms controlling this delicate balance in immune cells and consequent restriction of HSV-1 infection in these cells have not been completely elucidated. We have recently demonstrated that the transcription factor nuclear factor kappa B (NF-κB) can act as a main permissiveness regulator of HSV-1 infection in monocytic cells, however, mediators involved in this regulation have not been identified. To better define mechanisms involved in this phenomenon and, particularly, the possible involvement of ROS, wild type U937 cells or U937 cells stably transfected with a dominant-negative (DN) IκB-mutant and selenium-containing compounds, as anti-oxidants, were utilized. The main results can be summarized as follows. HSV-1 infection induces an immediate ROS production in U937 monocytic cells that can efficiently activate NF-κB but not in DN-IκB-mutant cells. Treatment with selenium-containing antioxidants efficiently inhibited HSV-1-induced ROS generation while producing increased levels of HSV-1 replication and a reduction of HSV-1-induced NF-κB activation in U937 monocytic cells. Our results suggest a scenario in which an efficient NF-κB-dependent ROS production in response to infection could contribute in limiting HSV-1 replication in monocytes/macrophages, thus avoiding possible irreparable damage to the innate immune system of the host during HSV-1 infection. MDPI 2019-05-10 /pmc/articles/PMC6563512/ /pubmed/31083280 http://dx.doi.org/10.3390/v11050428 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Marino-Merlo, Francesca
Papaianni, Emanuela
Frezza, Caterina
Pedatella, Silvana
De Nisco, Mauro
Macchi, Beatrice
Grelli, Sandro
Mastino, Antonio
NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells
title NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells
title_full NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells
title_fullStr NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells
title_full_unstemmed NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells
title_short NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells
title_sort nf-κb-dependent production of ros and restriction of hsv-1 infection in u937 monocytic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563512/
https://www.ncbi.nlm.nih.gov/pubmed/31083280
http://dx.doi.org/10.3390/v11050428
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