1. The antiviral RNAi response in vector and non-vector cells against orthobunyaviruses
- Author
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Dietrich, I, Shi, X, McFarlane, M, Watson, M, Blomström, AL, Skelton, JK, Kohl, A, Elliott, RM, Schnettler, E, Bausch, DG, and Bausch, D
- Subjects
0301 basic medicine ,Small interfering RNA ,Small RNA ,Viral Diseases ,Orthobunyavirus ,Epidemiology ,Molecular biology ,viruses ,Disease Vectors ,Ceratopogonidae ,Biochemistry ,Mosquitoes ,RNA interference ,Sequencing techniques ,Aedes ,Medicine and Health Sciences ,Small interfering RNAs ,RNA, Small Interfering ,lcsh:Public aspects of medicine ,virus diseases ,RNA sequencing ,3. Good health ,Enzymes ,Nucleic acids ,Insects ,RNA silencing ,Infectious Diseases ,Genetic interference ,Arboviral Infections ,Viruses ,Epigenetics ,Oxidoreductases ,Luciferase ,Research Article ,lcsh:Arctic medicine. Tropical medicine ,Arthropoda ,lcsh:RC955-962 ,Piwi-interacting RNA ,Biology ,Arbovirus ,Microbiology ,03 medical and health sciences ,Virology ,medicine ,Genetics ,Animals ,Non-coding RNA ,Biology and life sciences ,Public Health, Environmental and Occupational Health ,Organisms ,RNA ,Proteins ,lcsh:RA1-1270 ,medicine.disease ,Invertebrates ,Viral Replication ,Gene regulation ,Insect Vectors ,Research and analysis methods ,030104 developmental biology ,Molecular biology techniques ,Viral replication ,Enzymology ,Gene expression ,Arboviruses - Abstract
Background Vector arthropods control arbovirus replication and spread through antiviral innate immune responses including RNA interference (RNAi) pathways. Arbovirus infections have been shown to induce the exogenous small interfering RNA (siRNA) and Piwi-interacting RNA (piRNA) pathways, but direct antiviral activity by these host responses in mosquito cells has only been demonstrated against a limited number of positive-strand RNA arboviruses. For bunyaviruses in general, the relative contribution of small RNA pathways in antiviral defences is unknown. Methodology/Principal Findings The genus Orthobunyavirus in the Bunyaviridae family harbours a diverse range of mosquito-, midge- and tick-borne arboviruses. We hypothesized that differences in the antiviral RNAi response in vector versus non-vector cells may exist and that could influence viral host range. Using Aedes aegypti-derived mosquito cells, mosquito-borne orthobunyaviruses and midge-borne orthobunyaviruses we showed that bunyavirus infection commonly induced the production of small RNAs and the effects of the small RNA pathways on individual viruses differ in specific vector-arbovirus interactions. Conclusions/Significance These findings have important implications for our understanding of antiviral RNAi pathways and orthobunyavirus-vector interactions and tropism., Author Summary A number of orthobunyaviruses such as Oropouche virus, La Crosse virus and Schmallenberg virus are important global human or animal pathogens transmitted by arthropod vectors. Further understanding of the antiviral control mechanisms in arthropod vectors is key to developing novel prevention strategies based on preventing transmission. Antiviral small RNA pathways such as the exogenous siRNA and piRNA pathways have been shown to mediate antiviral activity against positive-strand RNA arboviruses, but information about their activities against negative-strand RNA arboviruses is critically lacking. Here we show that in Aedes aegypti-derived mosquito cells, the antiviral responses to mosquito-borne orthobunyaviruses is largely mediated by both siRNA and piRNA pathways, whereas the piRNA pathway plays only a minor role in controlling midge-borne orthobunyaviruses. This suggests that vector specificity is in part controlled by antiviral responses that depend on the host species. These findings contribute significantly to our understanding of arbovirus-vector interactions.
- Published
- 2017