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

IRCCS Centro Neurolesi Bonino-Pulejo, 98123 Messina, Italy
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Department of Chemical Sciences, University of Naples “Federico II”, 80126 Naples, Italy
Department of Science, University of Basilicata, 85100 Potenza, Italy
Department of Chemical Science and Technologies, University of Rome “Tor Vergata”, 00133 Rome, Italy
Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
The Institute of Translational Pharmacology, CNR, 00133 Rome, Italy
Author to whom correspondence should be addressed.
S.G. and A.M contributed equally as co-last authors to this study.
Viruses 2019, 11(5), 428;
Received: 1 April 2019 / Accepted: 8 May 2019 / Published: 10 May 2019
(This article belongs to the Section Animal Viruses)
PDF [4048 KB, uploaded 10 May 2019]


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. View Full-Text
Keywords: HSV-1; oxidative stress; NF-κB; innate response HSV-1; oxidative stress; NF-κB; innate response

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Marino-Merlo, F.; Papaianni, E.; Frezza, C.; Pedatella, S.; De Nisco, M.; Macchi, B.; Grelli, S.; Mastino, A. NF-κB-Dependent Production of ROS and Restriction of HSV-1 Infection in U937 Monocytic Cells. Viruses 2019, 11, 428.

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