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      Phleboviruses and the Type I Interferon Response

      review-article
      , *
      ,
      Viruses
      MDPI
      phlebovirus, NSs protein, interferon, RIG-I, PKR

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          Abstract

          The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host. NSs acts as antagonist of the antiviral type I interferon (IFN) system. Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.

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          Most cited references120

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          Enzootic hepatitis or rift valley fever. An undescribed virus disease of sheep cattle and man from east africa

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            IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA.

            Antiviral innate immunity relies on the recognition of microbial structures. One such structure is viral RNA that carries a triphosphate group on its 5' terminus (PPP-RNA). By an affinity proteomics approach with PPP-RNA as the 'bait', we found that the antiviral protein IFIT1 (interferon-induced protein with tetratricopeptide repeats 1) mediated binding of a larger protein complex containing other IFIT family members. IFIT1 bound PPP-RNA with nanomolar affinity and required the arginine at position 187 in a highly charged carboxy-terminal groove of the protein. In the absence of IFIT1, the growth and pathogenicity of viruses containing PPP-RNA was much greater. In contrast, IFIT proteins were dispensable for the clearance of pathogens that did not generate PPP-RNA. On the basis of this specificity and the great abundance of IFIT proteins after infection, we propose that the IFIT complex antagonizes viruses by sequestering specific viral nucleic acids.
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              Viral RNA detection by RIG-I-like receptors.

              In higher vertebrates, recognition of the non-self signature of invading viruses by genome-encoded pattern recognition receptors initiates antiviral innate immunity. Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) detect viral RNA as a non-self pattern in the cytoplasm and activate downstream signaling. Detection of viral RNA also activates stress responses resulting in stress granule-like aggregates, which facilitate RLR-mediated antiviral immunity. Among the three RLR family members RIG-I and melanoma differentiation-associated gene 5 (MDA5) recognize distinct viral RNA species with differential molecular machinery and activate signaling through mitochondrial antiviral signaling (MAVS, also known as IPS-1/VISA/Cardif), which leads to the expression of cytokines including type I and III interferons (IFNs) to restrict viral propagation. In this review, we summarize recent knowledge regarding RNA recognition and signal transduction by RLRs and MAVS/IPS-1. Copyright © 2015 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                22 June 2016
                June 2016
                : 8
                : 6
                : 174
                Affiliations
                Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Giessen 35392, Germany; wuerthje@ 123456staff.uni-marburg.de
                Author notes
                [* ]Correspondence: friedemann.weber@ 123456vetmed.uni-giessen.de ; Tel.: +49-641-99-383-50
                Article
                viruses-08-00174
                10.3390/v8060174
                4926194
                27338447
                2c5a5a61-65f2-4cbc-8df4-85520ca5f5df
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

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

                History
                : 08 May 2016
                : 20 June 2016
                Categories
                Review

                Microbiology & Virology
                phlebovirus,nss protein,interferon,rig-i,pkr
                Microbiology & Virology
                phlebovirus, nss protein, interferon, rig-i, pkr

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