The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis
The Flavivirus genus comprises many viruses (including dengue, Zika, West Nile and yellow fever viruses) which constitute important public health concerns worldwide. For several of these pathogens, neither antivirals nor vaccines are currently available. In addition to this unmet medical need, flavi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2018.00595/full |
| _version_ | 1818701402471399424 |
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| author | Clément Mazeaud Wesley Freppel Laurent Chatel-Chaix |
| author_facet | Clément Mazeaud Wesley Freppel Laurent Chatel-Chaix |
| author_sort | Clément Mazeaud |
| collection | DOAJ |
| description | The Flavivirus genus comprises many viruses (including dengue, Zika, West Nile and yellow fever viruses) which constitute important public health concerns worldwide. For several of these pathogens, neither antivirals nor vaccines are currently available. In addition to this unmet medical need, flaviviruses are of particular interest since they constitute an excellent model for the study of spatiotemporal regulation of RNA metabolism. Indeed, with no DNA intermediate or nuclear step, the flaviviral life cycle entirely relies on the cytoplasmic fate of a single RNA species, namely the genomic viral RNA (vRNA) which contains all the genetic information necessary for optimal viral replication. From a single open reading frame, the vRNA encodes a polyprotein which is processed to generate the mature viral proteins. In addition to coding for the viral polyprotein, the vRNA serves as a template for RNA synthesis and is also selectively packaged into newly assembled viral particles. Notably, vRNA translation, replication and encapsidation must be tightly coordinated in time and space via a fine-tuned equilibrium as these processes cannot occur simultaneously and hence, are mutually exclusive. As such, these dynamic processes involve several vRNA secondary and tertiary structures as well as RNA modifications. Finally, the vRNA can be detected as a foreign molecule by cytosolic sensors which trigger upon activation antiviral signaling pathways and the production of antiviral factors such as interferons and interferon-stimulated genes. However, to create an environment favorable to infection, flaviviruses have evolved mechanisms to dampen these antiviral processes, notably through the production of a specific vRNA degradation product termed subgenomic flavivirus RNA (sfRNA). In this review, we discuss the current understanding of the fates of flavivirus vRNA and how this is regulated at the molecular level to achieve an optimal replication within infected cells. |
| first_indexed | 2024-12-17T15:20:16Z |
| format | Article |
| id | doaj.art-387e302e15e2440cab2853761068d2e3 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-17T15:20:16Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-387e302e15e2440cab2853761068d2e32022-12-21T21:43:24ZengFrontiers Media S.A.Frontiers in Genetics1664-80212018-12-01910.3389/fgene.2018.00595418859The Multiples Fates of the Flavivirus RNA Genome During PathogenesisClément MazeaudWesley FreppelLaurent Chatel-ChaixThe Flavivirus genus comprises many viruses (including dengue, Zika, West Nile and yellow fever viruses) which constitute important public health concerns worldwide. For several of these pathogens, neither antivirals nor vaccines are currently available. In addition to this unmet medical need, flaviviruses are of particular interest since they constitute an excellent model for the study of spatiotemporal regulation of RNA metabolism. Indeed, with no DNA intermediate or nuclear step, the flaviviral life cycle entirely relies on the cytoplasmic fate of a single RNA species, namely the genomic viral RNA (vRNA) which contains all the genetic information necessary for optimal viral replication. From a single open reading frame, the vRNA encodes a polyprotein which is processed to generate the mature viral proteins. In addition to coding for the viral polyprotein, the vRNA serves as a template for RNA synthesis and is also selectively packaged into newly assembled viral particles. Notably, vRNA translation, replication and encapsidation must be tightly coordinated in time and space via a fine-tuned equilibrium as these processes cannot occur simultaneously and hence, are mutually exclusive. As such, these dynamic processes involve several vRNA secondary and tertiary structures as well as RNA modifications. Finally, the vRNA can be detected as a foreign molecule by cytosolic sensors which trigger upon activation antiviral signaling pathways and the production of antiviral factors such as interferons and interferon-stimulated genes. However, to create an environment favorable to infection, flaviviruses have evolved mechanisms to dampen these antiviral processes, notably through the production of a specific vRNA degradation product termed subgenomic flavivirus RNA (sfRNA). In this review, we discuss the current understanding of the fates of flavivirus vRNA and how this is regulated at the molecular level to achieve an optimal replication within infected cells.https://www.frontiersin.org/article/10.3389/fgene.2018.00595/fullflavivirusdengue virusZika virusWest Nile virusviral RNA replicationtranslation |
| spellingShingle | Clément Mazeaud Wesley Freppel Laurent Chatel-Chaix The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis Frontiers in Genetics flavivirus dengue virus Zika virus West Nile virus viral RNA replication translation |
| title | The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis |
| title_full | The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis |
| title_fullStr | The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis |
| title_full_unstemmed | The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis |
| title_short | The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis |
| title_sort | multiples fates of the flavivirus rna genome during pathogenesis |
| topic | flavivirus dengue virus Zika virus West Nile virus viral RNA replication translation |
| url | https://www.frontiersin.org/article/10.3389/fgene.2018.00595/full |
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