TY - JOUR
T1 - NF-ΚB-dependent production of ROS and restriction of HSV-1 infection in U937 monocytic cells
AU - Marino-Merlo, Francesca
AU - Papaianni, Emanuela
AU - Frezza, Caterina
AU - Pedatella, Silvana
AU - De Nisco, Mauro
AU - Macchi, Beatrice
AU - Grelli, Sandro
AU - Mastino, Antonio
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - HSV-1
KW - Innate response
KW - NF-ΚB
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85066060840&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066060840&partnerID=8YFLogxK
U2 - 10.3390/v11050428
DO - 10.3390/v11050428
M3 - Article
C2 - 31083280
AN - SCOPUS:85066060840
VL - 11
SP - 1
EP - 13
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 5
M1 - 428
ER -