Decoding the enigma of antiviral crisis: Does one target molecule regulate all?. (March 2019)

• Record Type: Journal Article
• Authors: Mahmud-Al-Rafat, Abdullah; Majumder, Apurba; Taufiqur Rahman, K.M.; Mahedi Hasan, A.M.; Didarul Islam, K.M.; Taylor-Robinson, Andrew W.; Billah, Md Morsaline
• Is Part Of: Cytokine. Volume 115(2019)
• Page Start: 13
• Page End: 23
• Publication Date: 2019-03
• Subjects: Virus -- Ebola -- SARS-CoV -- Dengue -- Cytokine storm -- Antiviral -- Pro-inflammatory response -- IL-6 -- ADAM-17; ACTH Adrenocorticotropic hormone -- ADAM-17 a disintegrin and metalloproteinase-17 -- ADE antibody-dependent enhancement -- ARDS acute respiratory distress syndrome -- BEBOV Bundibugyo Ebolavirus -- CCL5 chemokine (C-C motif) ligand -- CTLA-4 cytotoxic T-lymphocyte-associated protein 4 -- CXCL chemokine (C-X-C motif) ligand -- DC dendritic cell -- DENV dengue virus -- DF dengue fever -- DHF dengue hemorrhagic fever -- DIC disseminated intravascular coagulation -- DSS dengue shock syndrome -- EBOV Ebolavirus -- FasL/FasLG Fas ligand -- ICEBOV Ivory Coast Ebolavirus -- IFN interferon -- IFNAR interferon-α/β receptor -- IL-1RA interleukin-1 receptor antagonist -- IL interleukin -- IP-10 interferon gamma-induced protein 10 -- ISG interferon-stimulated gene -- GRO-α growth-regulated protein alpha -- M-CSF macrophage colony-stimulating factor -- MCP-1 monocyte chemotactic protein 1 -- MIF macrophage migration inhibitory factor -- MIP macrophage inflammatory protein -- MMP matrix metalloproteinases -- NF-kB nuclear factor kappa B -- NHP non-human primate -- PD-1 programmed cell death protein 1 -- RANTES regulated on activation normal T cell expressed and secreted -- REBOV Reston Ebolavirus -- rVSV-ZEBOV recombinant vesicular stomatitis virus–Zaire Ebola virus -- SARS severe acute respiratory syndrome -- SARS-CoV severe acute respiratory syndrome coronavirus -- SEBOV Sudan Ebolavirus -- TGF-1β transforming growth factor beta 1 -- TNF tumour necrosis factor -- TRAIL TNF-α related apoptosis-inducing ligand -- Treg T-regulatory cell -- VHF viral hemorrhagic fever -- ZEBOV Zaire Ebolavirus; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.12.008
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-6 class switching provides regulation over pro- and anti-inflammatory responses. Unregulated IL-6 trans-signaling promotes uncontrolled pro-inflammatory responses. ADAM-17 regulates class switching between IL-6 trans- and classical-signaling. Selective ADAM-17 blocking restricts overexpression of pro-inflammatory cytokines. ADAM-17 may be an antiviral drug target to reduce immunopathology disease severity. Abstract: Disease fatality associated with Ebola, SARS-CoV and dengue infections in humans is attributed to a cytokine storm that is triggered by excessive pro-inflammatory responses. Interleukin (IL)-6 acts as a mediator between pro- and anti-inflammatory reactivity by initiating trans- and classical-signaling, respectively. Hence, IL-6 is assumed to provide a target for a broad range of antiviral agents. Available immunosuppressive antivirals are directed to control an often exaggerated pro-inflammatory response that gives rise to complex clinical conditions such as lymphocytopenia. It is known that IL-6, via its soluble receptor (sIL-6R), initiates a pro-inflammatory response while an anti-inflammatory response is triggered by the membrane-bound IL-6 receptor (IL-6R). Future antivirals should thus aim to target the mechanism that regulates switching between IL-6 trans- and classical-signaling. In this review, we propose that the tumour necrosis factor-α converting enzyme ADAM-17 could be the master molecule involved in regulating IL-6 class switching and through this in controlling pro- and anti-inflammatory responses to viral antigenic stimuli. Therefore, ADAM-17 should be considered as a potential target molecule for novel antiviral drug discovery that would regulate host reactivity to infection and thereby limit or prevent fatal outcomes.