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      Functional RNA Structures in the 3′UTR of Tick-Borne, Insect-Specific and No-Known-Vector Flaviviruses

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      1 , 1 , 2 , 1 , 2 , *
      Viruses
      MDPI
      flavivirus, non-coding RNA, secondary structure

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          Abstract

          Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3 UTR of tick-borne, insect-specific and no-known-vector flaviviruses in silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs (xrRNAs) within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3 UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs.

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          Most cited references27

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          ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data

          The Environment for Tree Exploration (ETE) is a computational framework that simplifies the reconstruction, analysis, and visualization of phylogenetic trees and multiple sequence alignments. Here, we present ETE v3, featuring numerous improvements in the underlying library of methods, and providing a novel set of standalone tools to perform common tasks in comparative genomics and phylogenetics. The new features include (i) building gene-based and supermatrix-based phylogenies using a single command, (ii) testing and visualizing evolutionary models, (iii) calculating distances between trees of different size or including duplications, and (iv) providing seamless integration with the NCBI taxonomy database. ETE is freely available at http://etetoolkit.org
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            Phylogeny of the genus Flavivirus.

            We undertook a comprehensive phylogenetic study to establish the genetic relationship among the viruses of the genus Flavivirus and to compare the classification based on molecular phylogeny with the existing serologic method. By using a combination of quantitative definitions (bootstrap support level and the pairwise nucleotide sequence identity), the viruses could be classified into clusters, clades, and species. Our phylogenetic study revealed for the first time that from the putative ancestor two branches, non-vector and vector-borne virus clusters, evolved and from the latter cluster emerged tick-borne and mosquito-borne virus clusters. Provided that the theory of arthropod association being an acquired trait was correct, pairwise nucleotide sequence identity among these three clusters provided supporting data for a possibility that the non-vector cluster evolved first, followed by the separation of tick-borne and mosquito-borne virus clusters in that order. Clades established in our study correlated significantly with existing antigenic complexes. We also resolved many of the past taxonomic problems by establishing phylogenetic relationships of the antigenically unclassified viruses with the well-established viruses and by identifying synonymous viruses.
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              Insect-Specific Flaviviruses: A Systematic Review of Their Discovery, Host Range, Mode of Transmission, Superinfection Exclusion Potential and Genomic Organization

              There has been a dramatic increase in the number of insect-specific flaviviruses (ISFs) discovered in the last decade. Historically, these viruses have generated limited interest due to their inability to infect vertebrate cells. This viewpoint has changed in recent years because some ISFs have been shown to enhance or suppress the replication of medically important flaviviruses in co-infected mosquito cells. Additionally, comparative studies between ISFs and medically important flaviviruses can provide a unique perspective as to why some flaviviruses possess the ability to infect and cause devastating disease in humans while others do not. ISFs have been isolated exclusively from mosquitoes in nature but the detection of ISF-like sequences in sandflies and chironomids indicates that they may also infect other dipterans. ISFs can be divided into two distinct phylogenetic groups. The first group currently consists of approximately 12 viruses and includes cell fusing agent virus, Kamiti River virus and Culex flavivirus. These viruses are phylogenetically distinct from all other known flaviviruses. The second group, which is apparently not monophyletic, currently consists of nine viruses and includes Chaoyang virus, Nounané virus and Lammi virus. These viruses phylogenetically affiliate with mosquito/vertebrate flaviviruses despite their apparent insect-restricted phenotype. This article provides a review of the discovery, host range, mode of transmission, superinfection exclusion ability and genomic organization of ISFs. This article also attempts to clarify the ISF nomenclature because some of these viruses have been assigned more than one name due to their simultaneous discoveries by independent research groups.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                24 March 2019
                March 2019
                : 11
                : 3
                : 298
                Affiliations
                [1 ]Department of Theoretical Chemistry, University of Vienna, Währingerstraße 17, 1090 Vienna, Austria; romanoch@ 123456tbi.univie.ac.at (R.O.); ivo@ 123456tbi.univie.ac.at (I.L.H.)
                [2 ]Research Group BCB, Faculty of Computer Science, University of Vienna, Währingerstraße 29, 1090 Vienna, Austria
                Author notes
                Author information
                https://orcid.org/0000-0003-1126-0513
                https://orcid.org/0000-0001-7132-0800
                https://orcid.org/0000-0003-0925-5205
                Article
                viruses-11-00298
                10.3390/v11030298
                6466055
                30909641
                2d82756f-2ad6-42fc-8598-1868985a0a4d
                © 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
                : 01 March 2019
                : 20 March 2019
                Categories
                Article

                Microbiology & Virology
                flavivirus,non-coding rna,secondary structure
                Microbiology & Virology
                flavivirus, non-coding rna, secondary structure

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