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      Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

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          Abstract

          Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.

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          Most cited references212

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          On the origin of cancer cells.

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            RGD and other recognition sequences for integrins.

            Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
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              MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation.

              MicroRNAs (miRNAs) are small RNAs that function as posttranscriptional regulators of gene expression. miRNAs affect a variety of signaling pathways, and impaired miRNA regulation may contribute to the development of cancer and other diseases. Here we show that miRNA miR-10a interacts with the 5' untranslated region of mRNAs encoding ribosomal proteins to enhance their translation. miR-10a alleviates translational repression of the ribosomal protein mRNAs during amino acid starvation and is required for their translational induction following anisomycin treatment or overexpression of RAS. We show that miR-10a binds immediately downstream of the regulatory 5'TOP motif and that the 5'TOP regulatory complex and miR-10a are functionally interconnected. The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                18 January 2016
                January 2016
                : 8
                : 1
                : 23
                Affiliations
                [1 ]Biosciences, College of Life & Environmental Sciences, Geoffrey Pope Building, University of Exeter, Exeter, Devon EX4, UK; L.K.Bickley@ 123456exeter.ac.uk
                [2 ]European Union Reference Laboratory for Crustacean Diseases, Centre for Environment, Fisheries and Aquaculture Science (Cefas), Weymouth Laboratory, Weymouth, Dorset DT4 8UB, UK; ronny.vanaerle@ 123456cefas.co.uk (R.V.A.); kelly.bateman@ 123456cefas.co.uk (K.S.B.); grant.stentiford@ 123456cefas.co.uk (G.D.S.)
                Author notes
                [* ]Correspondence: bv213@ 123456exeter.ac.uk (B.V.); e.santos@ 123456exeter.ac.uk (E.M.S.); c.r.tyler@ 123456exeter.ac.uk (C.R.T.); Tel.: +44-(0)-1392-724607 (B.V.); +44-(0)-1392-724607 (E.M.S.); +44-(0)-1392-724450 (C.R.T.)
                [†]

                These authors contributed equally to this work.

                Article
                viruses-08-00023
                10.3390/v8010023
                4728583
                26797629
                fc5ab217-7d1a-4de3-979b-6f122459dde7
                © 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 by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 November 2015
                : 06 January 2016
                Categories
                Review

                Microbiology & Virology
                white spot syndrome virus,host–pathogen interactions,viral infection pathway,endocytosis,stress responses,apoptosis,treatments,mirna

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