Transgene-induced cell death following dengue-2 vi... - BV FAPESP
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Transgene-induced cell death following dengue-2 virus infection in Aedes aegypti

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Autor(es):
Carvalho, Danilo O. ; Costa-da-Silva, Andre L. ; Petersen, Vivian ; de Souza, Micael Santana ; Ioshino, Rafaella S. ; Marques, Isabel C. S. ; Franz, Alexander W. E. ; Olson, Ken E. ; James, Anthony A. ; Capurro, Margareth L.
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 13, n. 1, p. 11-pg., 2023-04-12.
Resumo

Dengue viruses (DENVs) are mosquito-borne flaviviruses causing millions of human infections each year and pose a challenge for public health systems worldwide. Aedes aegypti is the principal vector species transmitting DENVs to humans. Controlling Ae. aegypti is difficult due to the abundance of breeding sites and increasing insecticide resistance in the vector populations. Developing new vector control strategies is critical for decreasing the disease burden. One potential approach is genetically replacing Ae. aegypti populations with vector populations highly resistant to DENV transmission. Here, we focus on an alternative strategy for generating dengue 2 virus (DENV-2) resistance in genetically-modified Ae. aegypti in which the mosquitoes express an inactive form of Michelob_x (Mx), an antagonist of the Inhibitor of Apoptosis (IAP), to induce apoptosis in those cells in which actively replicating DENV-2 is present. The inactive form of Mx was flanked by the RRRRSAG cleavage motif, which was recognized by the NS2B/NS3 protease of the infecting DENV-2 thereby releasing and activating Mx which then induced apoptosis. Our transgenic strain exhibited a significantly higher mortality rate than the non-transgenic control when infected with DENV-2. We also transfected a DNA construct containing inactive Mx fused to eGFP into C6/36 mosquito cells and indirectly observed Mx activation on days 3 and 6 post-DENV-2 infections. There were clear signs that the viral NS2B/NS3 protease cleaved the transgene, thereby releasing Mx protein into the cytoplasm, as was confirmed by the detection of eGFP expression in infected cells. The present study represents proof of the concept that virus infection can be used to induce apoptosis in infected mosquito cells. (AU)

Processo FAPESP: 12/24105-3 - Imunobiologia de Leishmania spp.: estudo do papel de CD200 e biogênese do vacúolo parasitóforo em células fagocíticas infectadas por Leishmania
Beneficiário:Mauro Javier Cortez Véliz
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 20/13562-0 - Desvendando o papel do imune checkpoint ligante CD200 na infecção do hospedeiro por Leishmania spp.
Beneficiário:Mauro Javier Cortez Véliz
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/10254-1 - Promovendo mortalidade em Aedes aegypti infectado pelo vírus dengue
Beneficiário:Margareth de Lara Capurro-Guimarães
Modalidade de apoio: Auxílio à Pesquisa - Regular