Arbovirus-mosquito interactions: RNAi pathway

Abstract

Arthropod-borne (arbo) viruses infect hematophagous arthropods (vectors) to maintain virus transmission between vertebrate hosts. The mosquito vector actively controls arbovirus infection to minimize its fitness costs. The RNA interference (RNAi) pathway is the major antiviral response vectors use to restrict arbovirus infections. We know this because depleting RNAi gene products profoundly impacts arbovirus replication, the antiviral RNAi pathway genes undergo positive, diversifying selection and arboviruses have evolved strategies to evade the vector's RNAi responses. The vector's RNAi defense and arbovirus countermeasures lead to an arms race that prevents potential virus-induced fitness costs yet maintains arbovirus infections needed for transmission. This review will discuss the latest findings in RNAi-arbovirus interactions in the model insect (Drosophila melanogaster) and in specific mosquito vectors.

Figure 1

Antiviral siRNA response with proposed vector-virus interactions. Diagram showing components of the siRNA pathway in vectors during an antiviral response to a positive sense RNA virus: genomic viral positive sense RNA; long dsRNA generated by virus replication, dicer2 (Dcr2) which cleaves dsRNA, R2D2 a dsRNA binding protein, the RNA interference silencing complex (siRISC) that includes the guide RNA and argonaute 2 (Ago2), the effector in cleaving target viral RNA. In this diagram a model for persistent infections has been included using reverse transcription activity from endogenous retrotransposons of viral RNA to generate DNA forms as extrachromosomal DNAs (not shown) or the vector genome- integrated forms (shown). In this model, when the integrated DNA is transcribed, the RNA forms dsRNA in a manner not yet determined, although three possible ways of generating dsRNA are described. Once virus-specific cellular dsRNA is formed it can enter the siRNA pathway to control virus replication during the persistent state. Figure was modified from Figure 1 [60]

Figure 2

Antiviral piRNA response with proposed vector-virus interactions. Diagram showing components of the piRNA pathway in vectors during an antiviral response to a positive sense RNA virus: genomic viral positive sense RNA; virus-derived antisense RNA transcribed in nucleus, 24-27 nucleotide piRNAs loaded onto PIWI family proteins (Aub in Dm) in or near the nucleus and entry of primary piRNAs into the “ping-pong” amplification loop. In this model we have included reverse transcription activity from endogenous retrotransposons of viral RNA as a means of generating DNA forms as extrachromosomal DNAs (not shown) or the vector genome-integrated forms (shown) that may be transcribed to form the initial primary antisense RNA.