Antiviral responses of arthropod vectors: an update on recent advances

Abstract

Arthropod vectors, such as mosquitoes, ticks, biting midges and sand flies, transmit many viruses that can cause outbreaks of disease in humans and animals around the world. Arthropod vector species are invading new areas due to globalisation and environmental changes, and contact between exotic animal species, humans and arthropod vectors is increasing, bringing with it the regular emergence of new arboviruses. For future strategies to control arbovirus transmission, it is important to improve our understanding of virus-vector interactions. In the last decade knowledge of arthropod antiviral immunity has increased rapidly. RNAi has been proposed as the most important antiviral response in mosquitoes and it is likely to be the most important antiviral response in all arthropods. However, other newly-discovered antiviral strategies such as melanisation and the link between RNAi and the JAK/STAT pathway via the cytokine Vago have been characterised in the last few years. This review aims to summarise the most important and most recent advances made in arthropod antiviral immunity.

Keywords: Arbovirus; Innate immunity; Midge; Mosquito; RNAi; Tick.

Fig. 1

Innate immunity pathways in mosquitoes. Toll pathway PAMPs are recognised by extracellular PRRs which activate a proteolytic cascade leading to activation of the cytokine spaetzle by cleavage. Active spaetzle binds to the Toll receptor resulting in its dimerisation and a downstream signalling cascade results in the phosphorylation of Cactus, targeting it for degradation. Upon degradation of the negative regulator Cactus, REL1 translocates to the nucleus and activates transcription of effector genes. Imd pathway Binding of peptidoglycan of gram-negative bacteria to PRGP-like receptors activates Imd and a signal transduction cascade results in cleavage of Caspar from REL2, which translocates to the nucleus and activates transcription of AMPs. For both Toll and Imd it is unclear how these pathways become activated by viruses, but possible explanations are virus- or virus debris-associated PAMPs. JAK/STAT pathway Binding of the virus-induced cytokine Vago to an unknown cell surface receptor activates JAK, which in turn phosphorylates STAT. Phosphorylated STAT dimerises and translocates to the nucleus as a transcription factor. RNAi: Viral dsRNA molecules are recognised as foreign by Dcr-2 which cleaves the long dsRNA into 21 nt viRNAs. The viRNAs become incorporated into the RISC. The passenger strand of the viRNA is degraded and the RISC targets the viral genome/mRNA using the guide strand. Ago-2 slices the complementary target mRNA and inhibits synthesis of viral proteins. Viral dsRNA or ssRNA induces the production of piRNAs. Melanisation Mosquito pro-PO is activated by microorganisms such as bacteria and in some cases viruses. Activation of PO leads to the formation of melanin and in some cases PO activity is responsible for a reduction in infectious virus (whether or not this is due to melanin remains unclear)