Gaucherand, L.; Marie, H.; Cremaschi, J.; Pfeffer, S.

Bats are reservoirs for many viruses that frequently cause epidemics in humans and animals. It is thus critical to better understand their immune system and mechanisms of antiviral immunity. Despite an increasing number of studies, much is still unknown about the molecular mechanisms that govern bat-virus interactions, especially given the large diversity of bat species. Dicer is a conserved ribonuclease with multiple activities that can modulate antiviral immunity, including the detection of viral RNA as part of the RNA interference (RNAi) pathway, the maturation of micro RNAs, and the direct inhibition of innate immunity in mouse and human cells. In view of these complex activities of Dicer, we tested its antiviral activity in Myotis myotis nasal epithelial cells. Surprisingly, we did not see strong evidence of RNAi in these cells, but instead saw a proviral effect of Dicer for two alphaviruses, Sindbis and Semliki forest virus. We also observed a striking relocalization of Dicer to cytoplasmic foci upon infection with these viruses, which did not occur in the several human cell lines we tested. These foci contained dsRNA and viral plus strand RNA, suggesting that they are sites of viral replication. Finally, we found that factors specific to M. myotis cells are needed for Dicer relocalization. Overall, we propose that Dicer can play different roles in different bat species and/or cell types, and is being repurposed by alphaviruses to promote viral replication.