Abstract

RNA interference (RNAi) was shown over 18 years ago to be a mechanism by which arbovirus replication and transmission could be controlled in arthropod vectors. During the intervening period, research on RNAi has defined many of the components and mechanisms of this antiviral pathway in arthropods, yet a number of unexplored questions remain. RNAi refers to RNA-mediated regulation of gene expression. Originally, the term described silencing of endogenous genes by introduction of exogenous double-stranded (ds)RNA with the same sequence as the gene to be silenced. Further research has shown that RNAi comprises three gene regulation pathways that are mediated by small RNAs: the small interfering (si)RNA, micro (mi)RNA, and Piwi-interacting (pi)RNA pathways. The exogenous (exo-)siRNA pathway is now recognized as a major antiviral innate immune response of arthropods. More recent studies suggest that the piRNA and miRNA pathways might also have important roles in arbovirus-vector interactions. This review will focus on current knowledge of the role of the exo-siRNA pathway as an arthropod vector antiviral response and on emerging research into vector piRNA and miRNA pathway modulation of arbovirus-vector interactions. Although it is assumed that arboviruses must evade the vector’s antiviral RNAi response in order to maintain their natural transmission cycles, the strategies by which this is accomplished are not well defined. RNAi is also an important tool for arthropod gene knock-down in functional genomics studies and in development of arbovirus-resistant mosquito populations. Possible arbovirus strategies for evasion of RNAi and applications of RNAi in functional genomics analysis and arbovirus transmission control will also be reviewed.

Highlights

  • RNA-mediated gene silencing is an evolutionarily-conserved mechanism in which the presence of intracellular double-strandedRNA triggers a pathway that leads to the production of small RNAs that mediate regulation of expression of genes with cognate sequences to the RNA trigger [1]

  • The research reviewed here has given us a great deal of basic knowledge of the roles of RNA interference (RNAi) in interactions between arboviruses and vectors, and reveals a number of gaps that need to be filled for a fuller understanding

  • Deddouche et al [41] showed that Drosophila and Aedes Dicer 2 (Dcr2) are DExD/H-box helicases structurally related to RIG-I and MDA-5 of mammals, which are pattern recognition receptor (PRR) that recognize cytoplasmic viral RNAs and initiate type I interferon induction, a key antiviral innate immune response

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Summary

Introduction

RNA-mediated gene silencing is an evolutionarily-conserved mechanism in which the presence of intracellular double-stranded (ds)RNA triggers a pathway that leads to the production of small RNAs that mediate regulation of expression (usually inhibition) of genes with cognate sequences to the RNA trigger [1]. Pioneering plant research revealed the presence in primed plant cells of ~25 nt antisense RNAs thought to be specificity determinants of PTGS/VIGS/RNAi [7] and the observation that various viruses encode suppressors of gene silencing as counterdefenses to RNAi [8]. RNAi as a defense mechanism against viral or genomic parasites is broadly-distributed in invertebrates and plants; because of the close evolutionary relationship between Drosophila and mosquitoes, the fly has become a highly-studied model organism for understanding vector RNAi and its role in arbovirus infections. The distinct roles of these pathways are defense of the cell and organism against virus infection, regulation of development and gene expression, and defense of the genome against transposon mobilization and expression, respectively, cross-talk between pathways has been noted in Drosophila [9]. The role of the exo-siRNA pathway in arbovirusvector interactions has been most thoroughly studied; recent research has begun to shed light on potential roles of the piRNA and possibly miRNA pathways in vector modulation of arbovirus infections

The Exo-siRNA Pathway is an Antiviral Defense Mechanism in Arthropods
The piRNA Pathway and Arbovirus-Vector Interactions
Does the miRNA Pathway Have a Role in Arbovirus-Vector Interactions?
Arboviral Evasion of RNAi
RNAi as a Tool in Functional Genomics of Vectors
Harnessing Mosquito RNAi to Reduce Arbovirus Transmission
Concluding Remarks
Findings
Methods
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