Bat Dicer antiviral role and subcellular localization differ upon alphavirus infection in two distinct species

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 remains to be discovered 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 microRNAs, 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 slight 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 several human cell lines we tested. These foci contained dsRNA and viral plus strand RNA, suggesting that they are sites of viral replication. Importantly, there was no relocalization of Dicer upon infection in Tadarida brasiliensis lung epithelial cells that are known to have enhanced RNAi activity, suggesting a link between Dicer localization and antiviral activity. Finally, we found that factors specific to M. myotis cells are needed for Dicer relocalization, and that M. myotis Dicer has antiviral activity against Sindbis virus when expressed in human cells. Overall, we propose that Dicer can play different roles in distinct bat species and/or cell types, and that its antiviral role appears to be linked to its subcellular localization.