NF-ΚB-dependent production of ROS and restriction of HSV-1 infection in U937 monocytic cells

Francesca Marino-Merlo, Emanuela Papaianni, Caterina Frezza, Silvana Pedatella, Mauro De Nisco, Beatrice Macchi, Sandro Grelli, Antonio Mastino

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number428
Pages (from-to)1-13
Number of pages13
JournalViruses
Volume11
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • HSV-1
  • Innate response
  • NF-ΚB
  • Oxidative stress

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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