Dicer 2 mutations in Aedes aegypti cells lead to a diminished antiviral function against RVFV and BUNV infection

Mosquitoes are known to transmit different arthropod-borne (arbo-) viruses belonging to various virus families. The exogenous siRNA (exo-siRNA) pathway plays an important role in the mosquito defence against such virus infections, with Dicer 2 (Dcr2) as one of the key proteins that initiates the cleavage of viral dsRNAs into 21 nt long virus-derived small interfering RNAs (vsiRNAs). Previous data identified the importance of various motifs in Dcr2 for its siRNA-mediated antiviral activity. However, all this data focuses on plus-strand RNA viruses, although negative-strand RNA viruses, like Bunyavirales, include a lot of important mosquito-borne viruses. These viruses produce much fewer dsRNA molecules in the infected cells than their positive-strand RNA viral counter parts. Although the antiviral activity of the siRNA pathway and its key proteins (Dcr2 and Argonaute 2) have previously been reported, a lot of information is still lacking.