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Background  RNA interference (RNAi) is an important anti-viral defense mechanism. The  Aedes aegypti  genome encodes RNAi component orthologs, however, most populations of this mosquito are readily infected by, and subsequently transmit flaviviruses and alphaviruses. The goal of this study was to use  Ae. aegypti  as a model system to determine how the mosquito's anti-viral RNAi pathway interacts with recombinant Sindbis virus (SINV; family  Togaviridae , genus  Alphavirus ).    Results  SINV (TR339-eGFP) (+) strand RNA, infectious virus titers and infection rates transiently increased in mosquitoes following dsRNA injection to cognate  Ago2 ,  Dcr2 , or  TSN  mRNAs. Detection of SINV RNA-derived small RNAs at 2 and 7 days post-infection in non-silenced mosquitoes provided important confirmation of RNAi pathway activity. Two different recombinant SINV viruses (MRE16-eGFP and TR339-eGFP) with significant differences in infection kinetics were used to delineate vector/virus interactions in the midgut. We show virus-dependent effects on RNAi component transcript and protein levels during infection. Monitoring midgut  Ago2 ,  Dcr2 , and  TSN  transcript levels during infection revealed that only  TSN  transcripts were significantly increased in midguts over blood-fed controls. Ago2 protein levels were depleted immediately following a non-infectious bloodmeal and varied during SINV infection in a virus-dependent manner.    Conclusion  We show that silencing RNAi components in  Ae. aegypti  results in transient increases in SINV replication. Furthermore,  Ae. aegypti  RNAi is active during SINV infection as indicated by production of virus-specific siRNAs. Lastly, the RNAi response varies in a virus-dependent manner. These data define important features of RNAi anti-viral defense in  Ae. aegypti .

Aedes aegyptiuses RNA interference in defense against Sindbis virus infection