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Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions

The Flavivirus genus of the Flaviviridae family encompasses numerous enveloped plus-strand RNA viruses. Dengue virus (DENV), a flavivirus, is the leading cause of serious arthropod-borne disease globally. The genomes of DENV, like the genomes of yellow fever virus (YFV), West Nile fever virus (WNV),...

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Detalles Bibliográficos
Autores principales: Song, Yutong, Mugavero, JoAnn, Stauft, Charles B., Wimmer, Eckard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456755/
https://www.ncbi.nlm.nih.gov/pubmed/30967466
http://dx.doi.org/10.1128/mBio.00459-19
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author Song, Yutong
Mugavero, JoAnn
Stauft, Charles B.
Wimmer, Eckard
author_facet Song, Yutong
Mugavero, JoAnn
Stauft, Charles B.
Wimmer, Eckard
author_sort Song, Yutong
collection PubMed
description The Flavivirus genus of the Flaviviridae family encompasses numerous enveloped plus-strand RNA viruses. Dengue virus (DENV), a flavivirus, is the leading cause of serious arthropod-borne disease globally. The genomes of DENV, like the genomes of yellow fever virus (YFV), West Nile fever virus (WNV), or Zika virus (ZIKV), control their translation by a 5′-terminal capping group. Three other genera of Flaviviridae are remarkable because their viruses use internal ribosomal entry sites (IRESs) to control translation, and they are not arthropod transmitted. In 2006, E. Harris’ group published work suggesting that DENV RNA does not stringently need a cap for translation. They proposed that instead DENV translation is controlled by an interplay between 5′ and 3′ termini. Here we present evidence that the DENV or ZIKV 5′ untranslated regions (5′-UTRs) alone have IRES competence. This conclusion is based, first, on the observation that uncapped monocistronic mRNAs 5′ terminated with the DENV or ZIKV 5′-UTRs can efficiently direct translation of a reporter gene in BHK and C6/36 cells and second, that either 5′-UTR placed between two reporter genes can efficiently induce expression of the downstream gene in BHK cells but not in C6/36 cells. These experiments followed observations that uncapped DENV/ZIKV genomic transcripts, 5′ terminated with pppAN… or GpppAN…, can initiate infections of mammalian (BHK) or mosquito (C6/36) cells. IRES competence of the 5′-UTRs of DENV/ZIKV raises many open questions regarding the biology and control, as well as the evolution, of insect-borne flaviviruses.
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spelling pubmed-64567552019-04-12 Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions Song, Yutong Mugavero, JoAnn Stauft, Charles B. Wimmer, Eckard mBio Research Article The Flavivirus genus of the Flaviviridae family encompasses numerous enveloped plus-strand RNA viruses. Dengue virus (DENV), a flavivirus, is the leading cause of serious arthropod-borne disease globally. The genomes of DENV, like the genomes of yellow fever virus (YFV), West Nile fever virus (WNV), or Zika virus (ZIKV), control their translation by a 5′-terminal capping group. Three other genera of Flaviviridae are remarkable because their viruses use internal ribosomal entry sites (IRESs) to control translation, and they are not arthropod transmitted. In 2006, E. Harris’ group published work suggesting that DENV RNA does not stringently need a cap for translation. They proposed that instead DENV translation is controlled by an interplay between 5′ and 3′ termini. Here we present evidence that the DENV or ZIKV 5′ untranslated regions (5′-UTRs) alone have IRES competence. This conclusion is based, first, on the observation that uncapped monocistronic mRNAs 5′ terminated with the DENV or ZIKV 5′-UTRs can efficiently direct translation of a reporter gene in BHK and C6/36 cells and second, that either 5′-UTR placed between two reporter genes can efficiently induce expression of the downstream gene in BHK cells but not in C6/36 cells. These experiments followed observations that uncapped DENV/ZIKV genomic transcripts, 5′ terminated with pppAN… or GpppAN…, can initiate infections of mammalian (BHK) or mosquito (C6/36) cells. IRES competence of the 5′-UTRs of DENV/ZIKV raises many open questions regarding the biology and control, as well as the evolution, of insect-borne flaviviruses. American Society for Microbiology 2019-04-09 /pmc/articles/PMC6456755/ /pubmed/30967466 http://dx.doi.org/10.1128/mBio.00459-19 Text en Copyright © 2019 Song et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Song, Yutong
Mugavero, JoAnn
Stauft, Charles B.
Wimmer, Eckard
Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions
title Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions
title_full Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions
title_fullStr Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions
title_full_unstemmed Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions
title_short Dengue and Zika Virus 5′ Untranslated Regions Harbor Internal Ribosomal Entry Site Functions
title_sort dengue and zika virus 5′ untranslated regions harbor internal ribosomal entry site functions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456755/
https://www.ncbi.nlm.nih.gov/pubmed/30967466
http://dx.doi.org/10.1128/mBio.00459-19
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