Modulation of proinflammatory NF-κB signaling by ectromelia virus in RAW 264.7 murine macrophages

Macrophages are antigen-presenting cells (APCs) that play a crucial role in the innate immune response and may be involved in both clearance and spread of viruses. Stimulation of macrophages via Toll-like receptors (TLRs) results in activation of nuclear factor κB (NF-κB) and synthesis of proinflamm...

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Bibliographic Details
Published in:Archives of virology 2015-09, Vol.160 (9), p.2301-2314
Main Authors: Struzik, Justyna, Szulc-Dąbrowska, Lidia, Papiernik, Diana, Winnicka, Anna, Niemiałtowski, Marek
Format: Article
Language:English
Subjects:
Animals
Antigen-presenting cells
Biomedical and Life Sciences
Biomedicine
Cell Line
Cytokines
Cytokines - antagonists & inhibitors
drugs
Ectromelia virus
Ectromelia virus - immunology
IKappaB kinase
Immune clearance
Immune Evasion
Immune response
Infectious Diseases
Inflammation
Innate immunity
ligands
lipopeptides
Lipopolysaccharides
Lipopolysaccharides - immunology
Macrophages
Macrophages - immunology
Macrophages - virology
Medical Microbiology
Mice
NF-kappa B - metabolism
NF-κB protein
Nuclear transport
Original Article
Orthopoxvirus
pathogens
Phosphorylation
Poly I-C - immunology
Polyinosinic:polycytidylic acid
Poxviridae
Protein Transport
Signal Transduction
Therapeutic targets
TLR2 protein
TLR3 protein
TLR4 protein
Toll-like receptor 3
Toll-like receptor 4
Toll-like receptors
transcription factor NF-kappa B
vaccine development
Virology
Viruses
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Summary:Macrophages are antigen-presenting cells (APCs) that play a crucial role in the innate immune response and may be involved in both clearance and spread of viruses. Stimulation of macrophages via Toll-like receptors (TLRs) results in activation of nuclear factor κB (NF-κB) and synthesis of proinflammatory cytokines. In this work, we show modulation of proinflammatory NF-κB signaling by a member of the family Poxviridae, genus Orthopoxvirus – ectromelia virus (ECTV) – in RAW 264.7 murine macrophages. ECTV interfered with p65 NF-κB nuclear translocation induced by TLR ligands such as lipopolysaccharide (LPS) (TLR4), polyinosinic-polycytidylic acid (poly(I:C)) (TLR3) and diacylated lipopeptide Pam2CSK4 (TLR2/6). We observed that ECTV modulates phosphorylation of Ser32 of inhibitor of κB (IκBα) and Ser536 of p65. Interference of ECTV with TLR signaling pathways implied that proinflammatory cytokine synthesis was inhibited. Our studies provide new insights into the strategies of proinflammatory signaling modulation by orthopoxviruses during their replication cycle in immune cells. Understanding important immune interactions between viral pathogens and APCs might contribute to the identification of drug targets and the development of vaccines.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-015-2507-y