Dysregulation of miRNAs has broad impacts on virus infection in <i>Drosophila</i>

ABSTRACT Animal microRNAs (miRNAs) are important post-transcriptional regulators of gene expression. While the impact of certain miRNAs on viruses is well established, the frequency and magnitude of impacts more broadly are largely unknown. To address this, we screened the functional impact that the dysregulation of 34 individual miRNAs had on virus infection using a panel of three distinct RNA viruses: Drosophila C virus ( Dicistroviridae ), Flock House virus ( Nodaviridae ), and the arbovirus Sindbis virus ( Togaviridae ). We found that most of the 34 miRNA deletion mutant lines impacted infection of at least one virus, with close to half of the miRNA mutants impacting two or more. A wide variability and diversity in impacts on virus-induced mortality and viral RNA accumulation were also identified. Of those mutants that impacted the virus, the majority increased virus-induced mortality. Taken together, these results show that animal miRNAs play a broad and variable role in the dynamics of virus infection. IMPORTANCE A clear understanding of how host and virus interact is fundamental in developing techniques to reduce virus infection. Animal microRNAs (miRNAs) are a group of genetic regulators that have been shown to impact host and virus interactions. However, the frequency and magnitude to which miRNAs impact virus infection is still largely unknown. Here, we used a randomly selected panel of miRNA mutant Drosophila melanogaster fly populations to identify how often and variably miRNAs influence virus infection. Our findings reveal that a high proportion of miRNA mutants impacted virus, with close to half of them impacting multiple viruses. We also found a wide range of miRNA impacts on virus-induced mortality and viral RNA accumulation. Taken together, our results suggest that miRNAs play a common and variable role in the outcome of virus infection.