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Here, we show that transgenic overexpression of Dicer2 (<jats:italic>Dcr2<\/jats:italic>) or <jats:italic>R2d2<\/jats:italic> resulted in an accumulation of 21-nucleotide viral sequences that was accompanied by a significant suppression of dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) replication, thus indicating the broad-spectrum antiviral response mediated by the siRNA pathway that can be applied for the development of novel arbovirus control strategies. Interestingly, overexpression of <jats:italic>Dcr2<\/jats:italic> or <jats:italic>R2d2<\/jats:italic> regulated the mRNA abundance of a variety of antimicrobial immune genes, pointing to additional functions of DCR2 and R2D2 as well as cross-talk between the siRNA pathway and other immune pathways. Accordingly, transgenic overexpression of <jats:italic>Dcr2<\/jats:italic> or <jats:italic>R2d2<\/jats:italic> resulted in a lesser proliferation of the midgut microbiota and increased resistance to bacterial and fungal infections.<\/jats:p>","DOI":"10.1371\/journal.pbio.3001668","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T17:38:59Z","timestamp":1654796339000},"page":"e3001668","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Aedes aegypti siRNA pathway mediates broad-spectrum defense against human pathogenic viruses and modulates antibacterial and antifungal 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