Control of dengue virus in the midgut of Aedes aegypti by ectopic expression of the dsRNA-binding protein Loqs2
| Autor: | João Trindade Marques, Yaovi Mathias Honore Todjro, Eric R.G.R. Aguiar, Jean-Luc Imler, Tatiane C. Izidoro-Toledo, Thiago H. J. F. Leite, Marcele Neves Rocha, Simona Paro, Philippe Hammann, Juliana N. Armache, Fabiano Duarte Carvalho, Eric Marois, Isaque J. S. de Faria, Luciano Andrade Moreira, Siad C. G. Amadou, Elisa G. de Andrade, Caroline Dantas de Oliveira, Roenick P. Olmo, Lauriane Kuhn, Kátia P. Osório, Alvaro G. A. Ferreira, Kátia Paulino Ribeiro de Souza |
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| Rok vydání: | 2018 |
| Předmět: |
DNA Replication
0301 basic medicine Microbiology (medical) Small RNA Small interfering RNA viruses Immunology Mosquito Vectors Biology Dengue virus Virus Replication medicine.disease_cause Antiviral Agents Applied Microbiology and Biotechnology Microbiology Ectopic Gene Expression Animals Genetically Modified Dengue 03 medical and health sciences Aedes Genetics medicine Animals Drosophila Proteins Gene silencing Gene Silencing RNA Small Interfering RNA Double-Stranded fungi RNA-Binding Proteins virus diseases RNA Midgut Zika Virus Cell Biology Dengue Virus Cell biology Gastrointestinal Tract RNA silencing 030104 developmental biology Host-Pathogen Interactions RNA Viral Female Ectopic expression Carrier Proteins |
| Zdroj: | Nature Microbiology. 3:1385-1393 |
| ISSN: | 2058-5276 |
| Popis: | Dengue virus (DENV) is an arbovirus transmitted to humans by Aedes mosquitoes1. In the insect vector, the small interfering RNA (siRNA) pathway is an important antiviral mechanism against DENV2-5. However, it remains unclear when and where the siRNA pathway acts during the virus cycle. Here, we show that the siRNA pathway fails to efficiently silence DENV in the midgut of Aedes aegypti although it is essential to restrict systemic replication. Accumulation of DENV-derived siRNAs in the midgut reveals that impaired silencing results from a defect downstream of small RNA biogenesis. Notably, silencing triggered by endogenous and exogenous dsRNAs remained effective in the midgut where known components of the siRNA pathway, including the double-stranded RNA (dsRNA)-binding proteins Loquacious and r2d2, had normal expression levels. We identified an Aedes-specific paralogue of loquacious and r2d2, hereafter named loqs2, which is not expressed in the midgut. Loqs2 interacts with Loquacious and r2d2 and is required to control systemic replication of DENV and also Zika virus. Furthermore, ectopic expression of Loqs2 in the midgut of transgenic mosquitoes is sufficient to restrict DENV replication and dissemination. Together, our data reveal a mechanism of tissue-specific regulation of the mosquito siRNA pathway controlled by Loqs2. |
| Databáze: | OpenAIRE |
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