Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses

TLDR

Arboviruses are transmitted by both mosquitoes and ticks, and RNA interference is the primary antiviral defense in arthropods, yet the tick antiviral RNAi response remains poorly understood. This study aims to elucidate tick antiviral RNAi mechanisms to enable comparison with mosquito vectors. Using an Ixodes scapularis cell line, the authors identified key Argonaute proteins and demonstrated production of virus‑derived small interfering RNAs during Langat virus infection. They found that tick viRNAs are 22 nt long, preferentially map to viral termini, and that subgenomic flavivirus RNAs suppress tick RNAi, revealing distinct antiviral responses compared to mosquitoes.

Abstract

Arboviruses are transmitted by distantly related arthropod vectors such as mosquitoes (class Insecta) and ticks (class Arachnida). RNA interference (RNAi) is the major antiviral mechanism in arthropods against arboviruses. Unlike in mosquitoes, tick antiviral RNAi is not understood, although this information is important to compare arbovirus/host interactions in different classes of arbovirus vectos. Using an Ixodes scapularis-derived cell line, key Argonaute proteins involved in RNAi and the response against tick-borne Langat virus (Flaviviridae) replication were identified and phylogenetic relationships characterized. Analysis of small RNAs in infected cells showed the production of virus-derived small interfering RNAs (viRNAs), which are key molecules of the antiviral RNAi response. Importantly, viRNAs were longer (22 nucleotides) than those from other arbovirus vectors and mapped at highest frequency to the termini of the viral genome, as opposed to mosquito-borne flaviviruses. Moreover, tick-borne flaviviruses expressed subgenomic flavivirus RNAs that interfere with tick RNAi. Our results characterize the antiviral RNAi response in tick cells including phylogenetic analysis of genes encoding antiviral proteins, and viral interference with this pathway. This shows important differences in antiviral RNAi between the two major classes of arbovirus vectors, and our data broadens our understanding of arthropod antiviral RNAi.