The Antiviral RNAi Response in Vector and Non-vector Cells against Orthobunyaviruses.

Isabelle Dietrich,Anne-Lie Blomström,Alain Kohl,Jessica K Skelton,Esther Schnettler,Mick Watson,Richard M Elliott,Melanie Mcfarlane,Xiaohong Shi,Daniel G Bausch

doi:10.1371/journal.pntd.0005272

Isabelle Dietrich, Anne-Lie Blomström + Show 8 more

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https://doi.org/10.1371/journal.pntd.0005272

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Abstract

BackgroundVector 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 FindingsThe 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/SignificanceThese findings have important implications for our understanding of antiviral RNAi pathways and orthobunyavirus-vector interactions and tropism.

Highlights

Orthobunyaviruses are endemic in tropical and subtropical regions worldwide and are transmitted by mosquitoes, midges, ticks or other arthropods
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
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

Summary

Introduction

Orthobunyaviruses are endemic in tropical and subtropical regions worldwide and are transmitted by mosquitoes, midges, ticks or other arthropods. Like most viruses in the genus, the BUNV genome possesses a tripartite, singlestranded negative sense RNA genome, in which the small (S) segment encodes the nucleocapsid (N) protein and the nonstructural protein NSs in overlapping reading frames, the medium (M) segment encodes a viral glycoprotein precursor (in the order Gn-NSm-Gc) for two envelope glycoproteins Gn, Gc and a nonstructural protein NSm, and the large (L) segment encodes the RNA-dependent RNA polymerase. This genome structure is generally reflected by most orthobunyaviruses with some differences for example in the presence or length of NSs [1]. The relative contribution of small RNA pathways in antiviral defences is unknown

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