Control of dengue virus in the midgut of Aedes aegypti by ectopic expression of the dsRNA-binding protein Loqs2.

Autor: Olmo RP; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil.; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France., Ferreira AGA; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Izidoro-Toledo TC; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Aguiar ERGR; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., de Faria IJS; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil.; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France., de Souza KPR; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Osório KP; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Kuhn L; Plateforme Protéomique Strasbourg-Esplanade FRC 1589, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France., Hammann P; Plateforme Protéomique Strasbourg-Esplanade FRC 1589, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France., de Andrade EG; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil.; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France., Todjro YM; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Rocha MN; Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Instituto de Pesquisas René Rachou - Fiocruz, Belo Horizonte/MG, Brazil., Leite THJF; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Amadou SCG; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Armache JN; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil., Paro S; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France., de Oliveira CD; Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Instituto de Pesquisas René Rachou - Fiocruz, Belo Horizonte/MG, Brazil., Carvalho FD; Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Instituto de Pesquisas René Rachou - Fiocruz, Belo Horizonte/MG, Brazil., Moreira LA; Mosquitos Vetores: Endossimbiontes e Interação Patógeno-Vetor, Instituto de Pesquisas René Rachou - Fiocruz, Belo Horizonte/MG, Brazil., Marois E; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France., Imler JL; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France., Marques JT; Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte/MG, Brazil. jtm@ufmg.br.; Université de Strasbourg, CNRS UPR9022, Inserm U1257, Strasbourg, France. jtm@ufmg.br.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2018 Dec; Vol. 3 (12), pp. 1385-1393. Date of Electronic Publication: 2018 Oct 29.
DOI: 10.1038/s41564-018-0268-6
Abstrakt: Dengue virus (DENV) is an arbovirus transmitted to humans by Aedes mosquitoes 1 . In the insect vector, the small interfering RNA (siRNA) pathway is an important antiviral mechanism against DENV 2-5 . 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: MEDLINE
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