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      Emergence of a Novel Reassortant Strain of Bluetongue Serotype 6 in Israel, 2017: Clinical Manifestations of the Disease and Molecular Characterization

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          Abstract

          Reassortment contributes to the evolution of RNA viruses with segmented genomes, including Bluetongue virus (BTV). Recently, co-circulation of natural and vaccine BTV variants in Europe, and their ensuing reassortment, were proposed to promote appearance of novel European BTV strains, with potential implications for pathogenicity, spread and vaccination policies. Similarly, the geographical features of the Mediterranean basin, which spans over portions of three continents, may facilitate the appearance of clinically relevant reassortants via co-circulation of BTV strains of African, Asian and European origins. In August–October 2017, BTV serotype 6 (BTV-6) was identified in young animals exhibiting classical clinical signs of Bluetongue (BT) at Israeli sheep and cattle farms. Sequencing and pairwise analysis of this Israeli BTV-6 isolate revealed the closest sequence homology of its serotype-defining Segment 2 was with that of South African reference BTV-6 strain 5011 (93.88% identity). In contrast, the other viral segments showed highest homology (97.0%–99.47% identity) with BTV-3, -4 and -9 of Mediterranean and African origins. Specifically, four viral segments were nearly identical (99.13%–99.47%), with Tunisian and Italian BTV-3 strains (TUN2016 and SAD2018, correspondingly). Together, our data suggest that Mediterranean co-circulation and reassortment of BTV-3 and BTV-6 drove the emergence of a novel and virulent BTV-6 strain

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          Why do RNA viruses recombine?

          Key Points RNA viruses are able to undergo two forms of recombination: RNA recombination, which (in principle) can occur in any type of RNA virus, and reassortment, which is restricted to those viruses with segmented genomes. Rates of RNA recombination vary markedly among RNA viruses. Some viruses, particularly those with negative-sense single-stranded genomes, exhibit such low rates of recombination that they are effectively clonal. By contrast, some positive-sense single-stranded RNA viruses and some retroviruses such as HIV exhibit high rates of recombination that can exceed the rates of mutation when measured per nucleotide. Although recombination is often argued to represent a form of sexual reproduction, there is little evidence that recombination in RNA viruses evolved as a way of creating advantageous genotypes or removing deleterious mutations. In particular, there is no association between recombination frequency and the burden of a deleterious mutation. Similarly, there is little evidence that recombination could have been selected as a form of genetic repair. The strongest association for rates of recombination in RNA viruses is with genome structure. Hence, negative-sense single-stranded RNA viruses may recombine at low rates because of the restrictive association of genomic RNA in a ribonucleoprotein complex, as well as a lack of substrates for template switching, whereas some retroviruses recombine rapidly because their virions contain two genome copies and template switching between these copies is an inevitable part of the viral replication cycle. We therefore hypothesize that recombination in RNA viruses is a mechanistic by-product of the processivity of the viral polymerase that is used in replication, and that it varies with genome structure.
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            The pathology and pathogenesis of bluetongue.

            Bluetongue (BT) is an insect-transmitted viral disease of wild and domestic ruminants and, occasionally, other species. Amongst domestic livestock, BT is most common in certain breeds of sheep whereas asymptomatic BT virus (BTV) infection of cattle is typical in enzootic regions. BT in cattle can be a feature of specific outbreaks, notably the current epizootic in Europe caused by BTV serotype 8. BTV replicates within mononuclear phagocytic and endothelial cells, lymphocytes and possibly other cell types in lymphoid tissues, the lungs, skin and other tissues. Infected ruminants may exhibit a prolonged but not persistent viraemia and BTV is associated with erythrocytes during the late stages of this prolonged viraemia. The pathogenesis of BT involves injury to small blood vessels in target tissues, but the relative contributions of direct virus-induced cytolysis and virus-induced vasoactive mediators in causing endothelial injury and dysfunction are presently unclear. The lesions of BT are characteristic and include: haemorrhage and ulcers in the oral cavity and upper gastrointestinal tract; necrosis of skeletal and cardiac muscle; coronitis; subintimal haemorrhage in the pulmonary artery; oedema of the lungs, ventral subcutis, and fascia of the muscles of the neck and abdominal wall; and pericardial, pleural and abdominal effusions. Transplacental transmission of BTV in ruminants, with subsequent fetal infection, is a property of specific virus strains, especially those propagated in embryonated eggs or cell culture. The outcome of BTV infection of fetal ruminants is age-dependent, with distinctive cavitating lesions of the central nervous system in animals that survive infection in early gestation. Immune competence to BTV arises by mid-gestation, and animals infected in late gestation can be born viraemic and without significant brain malformations.
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              Culicoides and the emergence of bluetongue virus in northern Europe.

              In June 2006, bluetongue virus, an arboviral pathogen of ruminants, appeared in northern Europe for the first time, successfully overwintered and subsequently caused substantial losses to the farming sector in 2007 and 2008. This emergence served as a test of how the probability of arboviral incursion into new regions is assessed and has highlighted the reliance of decision making on paradigms that are not always underpinned by basic biological data. In this review, we highlight those areas of the epidemiology of bluetongue that are poorly understood, reflect upon why certain vital areas of research have received little attention and, finally, examine strategies that could aid future risk assessment and intervention.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                10 July 2019
                July 2019
                : 11
                : 7
                : 633
                Affiliations
                [1 ]Kimron Veterinary Institute, Division of Virology, Beit Dagan 50250, Israel
                [2 ]School of Molecular Cell Biology Biotechnology, Tel Aviv University, Tel Aviv 69978, Israel
                [3 ]Hachaklait veterinary services, Caesarea 3088900, Israel
                [4 ]Indi-Vet Ltd., Ashdod 7764933, Israel
                [5 ]Dr. Amos Bareli LTD, Kiryat Tiv’on 3605141, Israel
                [6 ]Lamikne veterinary services, Kiryat Tiv’on 3603247, Israel
                Author notes
                [* ]Correspondence: golendern@ 123456moag.gov.il (N.G.); marceloe@ 123456tauex.tau.ac.il (M.E.); Tel.: +972-3-9688949 (N.G.); +972-3-6409406 (M.E.); Fax: +972-3-9681788 (N.G.); + 972-3-6422046 (M.E.)
                Author information
                https://orcid.org/0000-0002-9074-7989
                Article
                viruses-11-00633
                10.3390/v11070633
                6669665
                31295819
                b6232abf-3734-49a2-9224-d6c9759e5e19
                © 2019 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
                : 14 May 2019
                : 09 July 2019
                Categories
                Article

                Microbiology & Virology
                bluetongue virus,orbivirus,reoviridae,sequencing,phylogenetic analysis,diagnostics,spread,descriptive epidemiology

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