The Role of Cytokines and Chemokines in Filovirus Infection

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.

Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles

“…It has been well documented that an eruption of cytokines, or a "cytokine storm, " often accompanies fatal cases of EBOV infection [6,8,86,87]. Specifically, cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), growth-regulated oncogene (GRO)-α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-15, IL-18, interferon (IFN)-α, -β, and -γ, IFN-inducible protein-10 (IP10), Eotaxin, monocyte chemoattractant protein (MCP)-1, macrophage-inflammatory protein (MIP)-1α and -1β, macrophage colony-stimulating factor (MCSF), RANTES, TGF-β1, TNF-α, and VEGF have all been implicated as differentially up-or downregulated during EBOV pathogenesis [8,[86][87][88][89]. This led us to question whether additional cytokines could potentially be present or upregulated in VP40 exosomes or EVs.…”

Perspectives towards antiviral drug discovery against Ebola virus

“…During disease prognosis, macrophages, monocytes, and dendritic cells are generally infected first, which later progressed to major cellular targets . The action of viral proteins (VP24 and VP35) causes suppression of type‐I interferon resulting in dysregulation of the immune response and activation of T‐cells as result of EBOV infection, with various disease manifestations …”

Elevated serum concentration of monocyte chemotactic protein 4 (MCP-4) as a novel non-invasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer

“…Cytokines are generally defined by their structure or function and include interleukins, growth factors, interferons, and chemokines . Chemokines have low molecular weights ranging from 7 to 15 kDa, and their function was first recognized as chemotactic activity on bone marrow‐derived cells .…”