In mammalian systems RNA can move between cells via vesicles. Here we demonstrate that the gastrointestinal nematodeHeligmosomoides polygyrus, which infects mice, secretes vesicles containing microRNAs (miRNAs) and Y RNAs as well as a nematode Argonaute protein. These vesicles are of intestinal origin and are enriched for homologues of mammalian exosome proteins. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergenAlternaria.Microarray analysis of mouse cells incubated with nematode exosomesin vitroidentifies Il33r and Dusp1 as suppressed genes, and Dusp1 can be repressed by nematode miRNAs based on a reporter assay. We further identify miRNAs from the filarial nematodeLitomosoides sigmodontisin the serum of infected mice, suggesting that miRNA secretion into host tissues is conserved among parasitic nematodes. These results reveal exosomes as another mechanism by which helminths manipulate their hosts and provide a mechanistic framework for RNA transfer between animal species.

The release of RNA‐containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA‐containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV‐RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA‐encoded messages affect signalling processes in EV‐targeted cells. Moreover, EV‐RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV‐RNA in vivo. These topics were discussed at the 2015 EV‐RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(‐RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV‐RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV‐RNA and calls for caution in interpretation of the obtained data.

RNA interference (RNAi) is an important defence against viruses and transposable elements (TEs). RNAi not only protects against viruses by degrading viral RNA, but hosts and viruses can also use RNAi to manipulate each other's gene expression, and hosts can encode microRNAs that target viral sequences. In response, viruses have evolved a myriad of adaptations to suppress and evade RNAi. RNAi can also protect cells against TEs, both by degrading TE transcripts and by preventing TE expression through heterochromatin formation. The aim of our review is to summarize and evaluate the current data on the evolution of these RNAi defence mechanisms. To this end, we also extend a previous analysis of the evolution of genes of the RNAi pathways. Strikingly, we find that antiviral RNAi genes, anti-TE RNAi genes and viral suppressors of RNAi all evolve rapidly, suggestive of an evolutionary arms race between hosts and parasites. Over longer time scales, key RNAi genes are repeatedly duplicated or lost across the metazoan phylogeny, with important implications for RNAi as an immune defence.

Drosophila melanogaster is a valuable invertebrate model for viral infection and antiviral immunity, and is a focus for studies of insect-virus coevolution. Here we use a metagenomic approach to identify more than 20 previously undetected RNA viruses and a DNA virus associated with wild D. melanogaster. These viruses not only include distant relatives of known insect pathogens but also novel groups of insect-infecting viruses. By sequencing virus-derived small RNAs, we show that the viruses represent active infections of Drosophila. We find that the RNA viruses differ in the number and properties of their small RNAs, and we detect both siRNAs and a novel miRNA from the DNA virus. Analysis of small RNAs also allows us to identify putative viral sequences that lack detectable sequence similarity to known viruses. By surveying >2,000 individually collected wild adult Drosophila we show that more than 30% of D. melanogaster carry a detectable virus, and more than 6% carry multiple viruses. However, despite a high prevalence of the Wolbachia endosymbiont—which is known to be protective against virus infections in Drosophila—we were unable to detect any relationship between the presence of Wolbachia and the presence of any virus. Using publicly available RNA-seq datasets, we show that the community of viruses in Drosophila laboratories is very different from that seen in the wild, but that some of the newly discovered viruses are nevertheless widespread in laboratory lines and are ubiquitous in cell culture. By sequencing viruses from individual wild-collected flies we show that some viruses are shared between D. melanogaster and D. simulans. Our results provide an essential evolutionary and ecological context for host–virus interaction in Drosophila, and the newly reported viral sequences will help develop D. melanogaster further as a model for molecular and evolutionary virus research. The fruit fly Drosophila melanogaster is extensively used as a model species for molecular biology and genetics. It is also widely studied for its evolutionary history, helping us understand how natural selection has shaped the genome. Drosophila research has been particularly valuable in determining how the insect immune system interacts with viruses and how co-evolution between hosts and viruses can shape the host immune system. Understanding insect–virus coevolution is important because some viruses—such as those which cause dengue and yellow fever in humans—also infect their insect vectors, and because the viruses of bees and other pollinators are implicated in pollinator decline. Although we have an increasingly good idea of how flies recognise and combat viral pathogens, we still have much to learn about the viruses they encounter and interact with in the wild. In this paper, we sequence all of the genetic material from a large collection of wild fruit flies and use it to identify more than 20 new viruses. We then survey individual wild flies and laboratory stocks to find out which viruses are common, which are rare, and which species of fruit fly they infect. Our results provide valuable tools and an evolutionary and ecological perspective that will help to improve Drosophila as a model for host–virus biology in the future.

Extracellular vesicles (EVs) have emerged as a ubiquitous mechanism for transferring information between cells and organisms across all three kingdoms of life. In addition to their roles in normal physiology, vesicles also transport molecules from pathogens to hosts and can spread antigens as well as infectious agents. Although initially described in the host-pathogen context for their functions in immune surveillance, vesicles enable multiple modes of communication by, and between, parasites. Here we review the literature demonstrating that EVs are secreted by intracellular and extracellular eukaryotic parasites, as well as their hosts, and detail the functional properties of these vesicles in maturation, pathogenicity and survival. We further describe the prospects for targeting or exploiting these complexes in therapeutic and vaccine strategies.

MicroRNAs (miRNAs) are small non-coding RNAs, 18–23 nucleotides long, which act as post-transcriptional regulators of gene expression. miRNAs are strongly implicated in the pathogenesis of many common diseases, including IBDs. This review aims to outline the history, biogenesis and regulation of miRNAs. The role of miRNAs in the development and regulation of the innate and adaptive immune system is discussed, with a particular focus on mechanisms pertinent to IBD and the potential translational applications.