siRNA targeting vaccinia virus double-stranded RNA binding protein [E3L] exert potent antiviral effects: Intersection with innate immune system

The Vaccinia virus gene, E3L, encodes a doublestrandedRNA [dsRNA]-binding protein. We hypothesizedthat, owing to the critical nature of dsRNA intriggering host innate antiviral responses, E3L-specificsmall-interfering RNAs siRNAs] should be effectiveantiviral agents against pox viruses, for whichVacciniavirus is an appropriate surrogate. In this study, we haveutilized two human cell types, namely, HeLa and 293T,one which responds to interferon [IFN]-β and the otherproduces and responds to IFN-β, respectively. The antiviraleffects were equally robust in HeLa and 293Tcells. However, in the case of 293T cells, several distinctfeatures were observed, when IFN-β is activatedin these cells. Vaccinia virus replication was inhibitedby 97% and 98% as compared to control infection inHeLa and 293T cells transfected with E3L-specific siRNAs,respectively. These studies demonstrate the utilityof E3L-specific siRNAs as potent antiviral agentsfor small pox and related pox viruses.