title: HSV-1-induced activation of NF-κB protects U937 monocytic cells against both virus replication and apoptosis.
abstract: The transcription factor nuclear factor-kappa B (NF-κB) is a crucial player of the antiviral innate response. Intriguingly, however, NF-κB activation is assumed to favour herpes simplex virus (HSV) infection rather than restrict it. Apoptosis, a form of innate response to viruses, is completely inhibited by HSV in fully permissive cells, but not in cells incapable to fully sustain HSV replication, such as immunocompetent cells. To resolve the intricate interplay among NF-κB signalling, apoptosis and permissiveness to HSV-1 in monocytic cells, we utilized U937 monocytic cells in which NF-κB activation was inhibited by expressing a dominant-negative IκBα. Surprisingly, viral production was increased in monocytic cells in which NF-κB was inhibited. Moreover, inhibition of NF-κB led to increased apoptosis following HSV-1 infection, associated with lysosomal membrane permeabilization. High expression of late viral proteins and induction of apoptosis occurred in distinct cells. Transcriptional analysis of known innate response genes by real-time quantitative reverse transcription-PCR excluded a contribution of the assayed genes to the observed phenomena. Thus, in monocytic cells NF-κB activation simultaneously serves as an innate process to restrict viral replication as well as a mechanism to limit the damage of an excessive apoptotic response to HSV-1 infection. This finding may clarify mechanisms controlling HSV-1 infection in monocytic cells.
authors: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina 98166, Italy.
authors: Francesca
authors: F
authors: Marino-Merlo
authors: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina 98166, Italy.
authors: Emanuela
authors: E
authors: Papaianni
authors: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina 98166, Italy.
authors: Maria Antonietta
authors: MA
authors: Medici
authors: Department of Systems Medicine, University of Rome "Tor Vergata", Rome 00133, Italy.
authors: Beatrice
authors: B
authors: Macchi
authors: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome 00133, Italy.
authors: Sandro
authors: S
authors: Grelli
authors: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina 98166, Italy.
authors: Claudia
authors: C
authors: Mosca
authors: Institute of Molecular Medicine and Cell Research, Albert Ludwigs University of Freiburg, Stefan Meier Strasse 17, Freiburg D-79104, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University of Freiburg, Albertstrasse 19a, Freiburg D-79104, Germany.|BIOSS, Centre for Biological Signaling Studies, Signalhaus, Schänzlestrasse 18, Freiburg D-79104, Germany.
authors: Christoph
authors: C
authors: Borner
authors: Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Messina 98166, Italy.|The Institute of Translational Pharmacology, CNR, Rome 00133, Italy.
authors: Antonio
authors: A
authors: Mastino
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D016898:Interferon-alpha / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D010539:Permeability; D011485:Protein Binding / Q000187:drug effects; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D020672:I-kappa B Proteins; D016898:Interferon-alpha; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004247:DNA