Identification of RNase L-Dependent, 3'-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells

Girardi, Erika; Chane-Woon-Ming, Béatrice; Messmer, Mélanie; Kaukinen, Pasi; Pfeffer, Sébastien

Altogether, our findings show a link between the host degradation pathway and stabilization of modified viral small RNAs. Clearly, not all the small RNAs identified by our deep sequencing approach correspond to RNase L downstream products. Nonetheless, the fact that at least some of these small RNAs are protected and detected might implicate them in signaling events, maybe upstream of the infection front, which might prove difficult to assess in cell culture. We hypothesized that by removing RNase L we might uncover signatures corresponding to other types of small RNAs, such as siRNAs or piRNAs, but it did not turn out to be the case. This could be due to the fact that other enzymes might also be involved in the production of RNA fragments and is an indication that it will make the detection of antiviral RNAi complicated in differentiated mammalian cells. An alternate hypothesis could also be that SINV encodes an RNA silencing suppressor that blocks Dicer activity but has no effect on RNase L. Finally, it is also possible that the antiviral RNAi response might be detected only in specific subtypes of cells in mammals, which would be different from the differentiated somatic cells we used for our study. Further investigation will be needed to answer these questions and to decipher the roles played by this type of virusderived small RNAs, as well as their potential implication in the design of new antiviral therapeutic strategies.