A novel coding-region RNA element modulates infectious dengue virus particle production in both mammalian and mosquito cells and regulates viral replication in Aedes aegypti mosquitoes
Abstract Dengue virus (DENV) is an enveloped flavivirus with a positive-sense RNA genome transmitted by Aedes mosquitoes, causing the most important arthropod-borne viral disease affecting humans. Relatively few cis -acting RNA regulatory elements have been described in the DENV coding-region. Here,...
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| Veröffentlicht in: | Virology (New York, N.Y.) N.Y.), 2012-10, Vol.432 (2), p.511-526 |
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| creator | Groat-Carmona, Anna Maria Orozco, Susana Friebe, Peter Payne, Anne Kramer, Laura Harris, Eva |
| description | Abstract Dengue virus (DENV) is an enveloped flavivirus with a positive-sense RNA genome transmitted by Aedes mosquitoes, causing the most important arthropod-borne viral disease affecting humans. Relatively few cis -acting RNA regulatory elements have been described in the DENV coding-region. Here, by introducing silent mutations into a DENV-2 infectious clone, we identify the conserved capsid-coding region 1 (CCR1), an RNA sequence element that regulates viral replication in mammalian cells and to a greater extent in Ae. albopictus mosquito cells. These defects were confirmed in vivo , resulting in decreased replication in Ae. aegypti mosquito bodies and dissemination to the salivary glands. Furthermore, CCR1 does not regulate translation, RNA synthesis or virion retention but likely modulates assembly, as mutations resulted in the release of non-infectious viral particles from both cell types. Understanding the role of CCR1 could help characterize the poorly-defined stage of assembly in the DENV life cycle and uncover novel anti-viral targets. |
| doi_str_mv | 10.1016/j.virol.2012.06.028 |
| format | Article |
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Relatively few cis -acting RNA regulatory elements have been described in the DENV coding-region. Here, by introducing silent mutations into a DENV-2 infectious clone, we identify the conserved capsid-coding region 1 (CCR1), an RNA sequence element that regulates viral replication in mammalian cells and to a greater extent in Ae. albopictus mosquito cells. These defects were confirmed in vivo , resulting in decreased replication in Ae. aegypti mosquito bodies and dissemination to the salivary glands. Furthermore, CCR1 does not regulate translation, RNA synthesis or virion retention but likely modulates assembly, as mutations resulted in the release of non-infectious viral particles from both cell types. 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Relatively few cis -acting RNA regulatory elements have been described in the DENV coding-region. Here, by introducing silent mutations into a DENV-2 infectious clone, we identify the conserved capsid-coding region 1 (CCR1), an RNA sequence element that regulates viral replication in mammalian cells and to a greater extent in Ae. albopictus mosquito cells. These defects were confirmed in vivo , resulting in decreased replication in Ae. aegypti mosquito bodies and dissemination to the salivary glands. Furthermore, CCR1 does not regulate translation, RNA synthesis or virion retention but likely modulates assembly, as mutations resulted in the release of non-infectious viral particles from both cell types. 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| ispartof | Virology (New York, N.Y.), 2012-10, Vol.432 (2), p.511-526 |
| issn | 0042-6822 1096-0341 |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Aedes - virology Aedes aegypti Aedes aegypti mosquitoes Amino Acid Sequence Animals Assembly Base Sequence Capsid Proteins - chemistry Capsid Proteins - genetics Capsid Proteins - metabolism Cell Line Cells, Cultured cis-acting RNA regulatory element Cricetinae Dengue virus Dengue Virus - genetics Dengue Virus - metabolism Flavivirus Gene Expression Regulation, Viral Infectious Disease Molecular Sequence Data Regulatory Sequences, Ribonucleic Acid RNA, Viral - genetics RNA, Viral - metabolism Viral replication Virion - metabolism Virus Replication |
| title | A novel coding-region RNA element modulates infectious dengue virus particle production in both mammalian and mosquito cells and regulates viral replication in Aedes aegypti mosquitoes |
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