Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-Deficient Mice Is Due to Impaired miR24 and miR93 Expression

Otsuka, M., et al. 2007. Immunity. 27:123-134.

Speaker: Yu-Lun Cheng (鄭宇倫)                                                   Time: 15:00~16:00, Oct. 31, 2007

Commentator: Dr. Shun-Hua Chen (陳舜華老師)                          Place: Room 601

Abstract:

        Dicer, an RNase III enzyme, is essential for processing small RNA regulatory. Small RNA regulatory has two classes: one is exogenous siRNA and the other is endogenous miRNA. Although Dicer processes double-strand viral RNA into siRNAs which inhibit viral replication [1-4], siRNA derived from viral genomes have not been reported in mammals. So authors generate Dicer1 deficient mice to research the effect on viral susceptibility. It is result that Dicer1 deficient mice infected vesicular stomatitis virus (VSV) exhibit reduced survival rates. Dicer1^-/- macrophages infected VSV increase the viral titer, RNA expression, and protein compared to wild-type, but no accumulations of cytokines transcripts and proteins. Next, authors constructed report plasmids fused different proteins of the VSV sequence to examine which region yield mRNA targeted by miRNA. According data and software predicted, there are probable four candidate miRNAs in three regions. By anti-candidate miRNAs, all of these candidates locate in the VSV L and P genes which encode the viral RNA-dependent RNA polymerase and a polymerase cofactor. And two of them, miR24 and miR93, can interfere with VSV replication. Finally, authors create two VSV mutants that can be not targeted by candidate miRNAs. The results confirm that miR24 and miR93 are responsible for the Dicer1-mediated suppression of VSV replication in wild-type macrophages. In other words, impaired miR24 and miR93 caused by Dicer1-deficiency increase in susceptibility to VSV in Dicer1^-/- mice.

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