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

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Abstract

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.

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Acknowledgments

We thank Dr. Felix N. Toka (from WULS-SGGW) for help with manuscript editing. This work was supported by Grant No. N N308573740 (for M.N.) from the Ministry of Science and Higher Education in Warsaw, Grant No. 2011/03/B/NZ6/03856 (for M.N.) from National Science Center in Cracow and internal research Grant No. 505 1002340034 (for L.S.D.) and No. 505 1002340050 (for J.S.) from WULS-SGGW in Warsaw.

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  1. Diana Papiernik

    Present address: Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wrocław, Poland

Authors and Affiliations

  1. Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Ciszewskiego 8, 02-786, Warsaw, Poland

    Justyna Struzik, Lidia Szulc-Dąbrowska, Diana Papiernik & Marek Niemiałtowski

  2. Department of Pathology and Veterinary Diagnostics, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Nowoursynowska 159c, 02-776, Warsaw, Poland

    Anna Winnicka

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  1. Justyna Struzik
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Correspondence to Lidia Szulc-Dąbrowska.

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J. Struzik and L. Szulc-Dąbrowska contributed equally to this study.

M. Niemiałtowski: Deceased.

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Struzik, J., Szulc-Dąbrowska, L., Papiernik, D. et al. Modulation of proinflammatory NF-κB signaling by ectromelia virus in RAW 264.7 murine macrophages. Arch Virol 160, 2301–2314 (2015). https://doi.org/10.1007/s00705-015-2507-y

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