The impact of
influenza infection is a major public health concern. Significant morbidity and
mortality is associated with infection especially in susceptible populations
such as the elderly. Efforts to improve vaccine efficacy and long-term
immunological memory are currently areas of significant research interest. It
is predicted that over 30% of all human genes are targeted by microRNAs
(miRNAs), including many immune related genes. For this reason, the artificial
use of miRNAs for RNA interference (RNAi) is a rapidly emerging field. However,
key limitations exist within the field; most notably delivery of miRNAs to the
desired target cell populations
in vivo.
The suppressors of cytokine signaling (SOCS) proteins are important in the
regulation of cytokine production, with SOCS1 and SOCS3 having key roles in innate
immunity. miR-155 directly targets SOCS1 and is implicated in the proliferation
of various T-cell subsets. This study utilised an influenza A based delivery
system to express miR-155 in order to target SOCS1 mRNA in infected cells.
Using real time PCR (qPCR), dual luciferase and western blot technology we show
that miR-155 delivery resulted in a significant increase in cellular miR-155
levels that facilitated a significant decrease in SOCS1 gene expression and a
functional increase in IL-6 and IFN-β cytokines. Further
in vivo studies have shown that this system is capable of enhancing
various aspects of the influenza A specific immune responses
in mice.