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      The Role of Cytokines and Chemokines in Filovirus Infection

      review-article
      * ,
      Viruses
      MDPI
      Filovirus, Ebola, Marburg, cytokine, chemokine, immunopathology

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          Abstract

          Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology.

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          Most cited references105

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          Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu.

          Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein-based tethers, which we term 'tetherins', that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS.
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            TNF-mediated inflammatory disease.

            JR Bradley (2008)
            TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response. This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease. TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways. These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration. Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis. The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis. The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases. 2007 Pathological Society of Great Britain and Ireland
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              Chemokines: a new classification system and their role in immunity.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                23 October 2015
                October 2015
                : 7
                : 10
                : 5489-5507
                Affiliations
                United States Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD 21702, USA; arthur.j.goff.civ@ 123456mail.mil
                Author notes
                [* ]Correspondence: sandra.l.bixler.ctr@ 123456mail.mil ; Tel.: +1-301-619-3014; Fax: +1-301-619-2290
                Article
                viruses-07-02892
                10.3390/v7102892
                4632400
                26512687
                e4c04a6f-fb52-438f-b5e3-72896992d5de
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 September 2015
                : 14 October 2015
                Categories
                Review

                Microbiology & Virology
                filovirus,ebola,marburg,cytokine,chemokine,immunopathology
                Microbiology & Virology
                filovirus, ebola, marburg, cytokine, chemokine, immunopathology

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