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

Abstract

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.

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells

“…It was shown that HSV-1 infection quickly induced intracellular ROS that were necessary for proper activation of innate antiviral immune responses [37]. Initial generation of ROS post virus infection acts as a microbicidal compound to regulate several processes, such as expression of innate-response-related genes, NF-κB activation, inflammasome activation, autophagy and programmed necrosis [38–40]. However, its overproduction may exacerbate downstream inflammatory responses as well as oxidative injury depending on the absolute intracellular levels of ROS and other reactive species [16, 41].…”

Quercus acuta Thunb. (Fagaceae) and Its Component, Isoquercitrin, Inhibit HSV-1 Replication by Suppressing Virus-Induced ROS Production and NF-κB Activation

“…According to previous studies, NF-κB activation is one of the main mechanisms present in HSV-1-infected cells and is known to be closely related to ROS production [27]. Therefore, we checked whether the inhibition of NF-κB activation is also associated with ROS generation in QA-treated cells infected with HSV-1.…”

Infection of Endothelial Cells by Dengue Virus Induces ROS Production by Different Sources Affecting Virus Replication, Cellular Activation, Death and Vascular Permeability

“…Despite possible antiviral effects of oxidative stress responses (49,50), we observed that ROS inhibition reduced DENV replication in HBMEC. Different mechanisms might explain this phenomenon.…”