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      Viral RNA Silencing Suppression: The Enigma of Bunyavirus NSs Proteins

      review-article
      , *
      Viruses
      MDPI
      RNAi, RNA silencing, innate immunity, bunyavirus, NSs, tospovirus, orthobunyavirus, RNA silencing suppression

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          Abstract

          The Bunyaviridae is a family of arboviruses including both plant- and vertebrate-infecting representatives. The Tospovirus genus accommodates plant-infecting bunyaviruses, which not only replicate in their plant host, but also in their insect thrips vector during persistent propagative transmission. For this reason, they are generally assumed to encounter antiviral RNA silencing in plants and insects. Here we present an overview on how tospovirus nonstructural NSs protein counteracts antiviral RNA silencing in plants and what is known so far in insects. Like tospoviruses, members of the related vertebrate-infecting bunyaviruses classified in the genera Orthobunyavirus, Hantavirus and Phlebovirus also code for a NSs protein. However, for none of them RNA silencing suppressor activity has been unambiguously demonstrated in neither vertebrate host nor arthropod vector. The second part of this review will briefly describe the role of these NSs proteins in modulation of innate immune responses in mammals and elaborate on a hypothetical scenario to explain if and how NSs proteins from vertebrate-infecting bunyaviruses affect RNA silencing. If so, why this discovery has been hampered so far.

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          Most cited references141

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          Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways.

          The RNase III enzyme Dicer processes RNA into siRNAs and miRNAs, which direct a RNA-induced silencing complex (RISC) to cleave mRNA or block its translation (RNAi). We have characterized mutations in the Drosophila dicer-1 and dicer-2 genes. Mutation in dicer-1 blocks processing of miRNA precursors, whereas dicer-2 mutants are defective for processing siRNA precursors. It has been recently found that Drosophila Dicer-1 and Dicer-2 are also components of siRNA-dependent RISC (siRISC). We find that Dicer-1 and Dicer-2 are required for siRNA-directed mRNA cleavage, though the RNase III activity of Dicer-2 is not required. Dicer-1 and Dicer-2 facilitate distinct steps in the assembly of siRISC. However, Dicer-1 but not Dicer-2 is essential for miRISC-directed translation repression. Thus, siRISCs and miRISCs are different with respect to Dicers in Drosophila.
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            Insect vector interactions with persistently transmitted viruses.

            The majority of described plant viruses are transmitted by insects of the Hemipteroid assemblage that includes aphids, whiteflies, leafhoppers, planthoppers, and thrips. In this review we highlight progress made in research on vector interactions of the more than 200 plant viruses that are transmitted by hemipteroid insects beginning a few hours or days after acquisition and for up to the life of the insect, i.e., in a persistent-circulative or persistent-propagative mode. These plant viruses move through the insect vector, from the gut lumen into the hemolymph or other tissues and finally into the salivary glands, from which these viruses are introduced back into the plant host during insect feeding. The movement and/or replication of the viruses in the insect vectors require specific interactions between virus and vector components. Recent investigations have resulted in a better understanding of the replication sites and tissue tropism of several plant viruses that propagate in insect vectors. Furthermore, virus and insect proteins involved in overcoming transmission barriers in the vector have been identified for some virus-vector combinations.
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              RNA-based antiviral immunity.

              In eukaryotic RNA-based antiviral immunity, viral double-stranded RNA is recognized as a pathogen-associated molecular pattern and processed into small interfering RNAs (siRNAs) by the host ribonuclease Dicer. After amplification by host RNA-dependent RNA polymerases in some cases, these virus-derived siRNAs guide specific antiviral immunity through RNA interference and related RNA silencing effector mechanisms. Here, I review recent studies on the features of viral siRNAs and other virus-derived small RNAs from virus-infected fungi, plants, insects, nematodes and vertebrates and discuss the innate and adaptive properties of RNA-based antiviral immunity.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                23 July 2016
                July 2016
                : 8
                : 7
                : 208
                Affiliations
                Laboratory of Virology, Department of Plant Sciences, Wageningen University, Wageningen, 6708PB, The Netherlands; marcio.hedil@ 123456outlook.com
                Author notes
                [* ]Correspondence: richard.kormelink@ 123456wur.nl ; Tel.: +31-317483085
                Article
                viruses-08-00208
                10.3390/v8070208
                4974542
                27455310
                44fa2bc1-6cba-4c5e-a2c1-acca11529c9d
                © 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
                : 09 June 2016
                : 19 July 2016
                Categories
                Review

                Microbiology & Virology
                rnai,rna silencing,innate immunity,bunyavirus,nss,tospovirus,orthobunyavirus,rna silencing suppression

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