Mosquito cells support RNAi and homologues of the Drosophila RNAi components are encoded by the recently sequenced genome of Anopheles gambiae, which transmits both malaria and o'nyong-nyong alphavirus (Christophides et al., 2002; Hoa et al., 2003; Holt et al., 2002; Levashina et al., 2001; Powers et al., 2000). It has been demonstrated recently that replicating virus RNAs are naturally targeted for destruction by RNAi in mosquito cells (Li et al., 2004). This potent RSAR does not require prior activation, e.g. through transformation with an inverted-repeat RNA transgene (Adelman et al., 2002), but it is masked in A. gambiae cells by the action of the B2 protein expressed from wild-type NoV RNA1. After its B2 was made untranslatable, the accumulation of NoV RNAs was almost completely abolished in mosquito cells (Li et al., 2004). The NoV RNA1 mutant was rescued by co-transfection with a plasmid expressing B2 of either nodavirus, a dsRNA or siRNA targeting the mRNA of the A. gambiae AGO2, but not by an unrelated dsRNA or siRNA. Thus, as has been found in Drosophila, NoV RNA replication also triggers RSAR in A. gambiae cells which is both AGO2-dependent and sensitive to B2 suppression. These findings establish RSAR as a new RNA-based antiviral immunity in mosquitoes.
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