West Nile virus (WNV) is an enveloped virus with a single-stranded positive-sense
RNA genome from the Flaviviridae family. WNV is spread by mosquitoes and able to infect humans, causing
encephalitis and
meningitis that can be fatal; it therefore presents a significant risk for human health. In insects, innate response to
RNA virus infection mostly relies on RNA interference and JAK/SAT pathways; however, some evidence indicates that it can also involve
microRNAs (
miRNAs).
miRNAs are small noncoding RNAs that regulate gene expression at posttranscriptional level and play an important role in a number of processes, including immunity and
antiviral response. In this study, we focus on the
miRNA-mediated response to WNV in mosquito cells. We demonstrate that in response to
WNV infection the expression of a mosquito-specific
miRNA, aae-miR-2940, is selectively downregulated in Aedes albopictus cells. This
miRNA is known to upregulate the
metalloprotease m41 FtsH gene, which we have also shown to be required for efficient WNV replication. Correspondingly, downregulation of aae-miR-2940 reduced the
metalloprotease level and restricted WNV replication. Thus, we have identified a novel
miRNA-dependent mechanism of
antiviral response to WNV in mosquitoes.
IMPORTANCE: A detailed understanding of vector-pathogen interactions is essential to address the problems posed by
vector-borne diseases. Host and viral
miRNAs play an important role in regulating expression of viral and host genes involved in endogenous processes, including
antiviral response. There has been no evidence to date for the role of mosquito
miRNAs in response to flaviviruses. In this study, we show that downregulation of aae-miR-2940 in mosquito cells acts as a potential
antiviral mechanism in the mosquito host to inhibit WNV replication by repressing the expression of the
metalloprotease m41 FtsH gene, which is required for efficient WNV replication. This is the first identification of an
miRNA-dependent
antiviral mechanism in mosquitoes, which inhibits replication of WNV. Our findings should facilitate identification of targets in the mosquito genome that can be utilized to suppress vector population and/or limit WNV replication.