Rabies virus infection and microRNAs.

Endogenous RNA-silencing mechanisms have been shown to play a role in regulating viral and host processes during the course of infection. Such interactive processes may involve host cellular and/or viral-encoded microRNAs (miRNAs). Rabies is unique not only in terms of its invariably fatal course once disease signs develop, but it also has a variable incubation period (eclipse phase). It has been recently shown that cells or tissues of different origin have their own specific miRNAs that, in theory, may impact on viral transcription and replication. This may possibly explain, in part, why rabies virus remains dormant at the inoculation site in rabies patients for long periods. Owing to the RNA interference (RNAi) technology, it has been possible to introduce exogenously designed artificial short interfering RNAs (siRNAs) and miRNAs into virus-infected cells for therapeutic purposes. Successful attempts in using RNAi for prevention and treatment of DNA and RNA virus infections both in vitro and in vivo experiments have been reported. The fact that rabies remains incurable has stimulated the development of the therapeutic RNAi strategy. We describe herein preliminary evidence that cellular miRNA may play a role in suppressing viral replication, explaining the eclipse phase, and that artificially designed multitargeting miRNA can successfully inhibit rabies virus transcription and replication in vitro.