The Journal of Virology recently released an online ahead of print article by NIH researchers Giulia Fabozzi and colleagues regarding Ebolavirus "resistance" to RNAi.
RNA interference (RNAi) is thought to have evolved as a eukaryotic cellular defense response to viral infections and transposons. As such, the introduction of small "interfering" (si) double-stranded RNA triggers a sequence-specific response in which the corresponding mRNA transcript is degraded before translation can occur. This results in "silencing" of the corresponding gene.
In this study, as Fabozzi et al. argue, Ebolavirus (EBOV) has evolved a mechanism to revert host cell attempts to eradicate viral proteins. After designing siRNAs to EBOV genes they found that the siRNAs were ineffective at silencing during active viral replication but did silence when the genes were transiently expressed in mammalian cells. Using a series of reporter-based RNAi assays, they identified three viral ribonucleoproteins (RNP) that can revert silencing for viral and a GFP reporter independent of interferon activation. This observation was dose dependent on the amount of plasmid (and ultimately expressed gene product) that was co-transfected. They also examined these suppressors of RNA silencing (SRS) interactions with RNAi effector machinery Dicer, PACT and TRBP and attempted a mutagenesis analysis. Thus, this illustrates the continued evolution and antagonism between cells and viruses.
Looks like it's your move now, eukaryotes.
Fabozzi G, Nabel CS, Dolan MA, Sullivan NJ. Ebolavirus Proteins Suppress siRNA Effects by Direct Interaction with the Mammalian RNAi Pathway. J Virol. 2011 Jan 12. [Epub ahead of print]
- Vy Tran