Project description:Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe clinical symptoms and mortality in humans. Haemaphysalis longicornis tick has been identified as the competent vector for SFTSV transmission. Although antiviral RNA interference (RNAi) in insects has been well documented, the degree to which RNAi contributes to antiviral defense in ticks is still largely elusive. In this study, utilizing arthropod-borne RNA viruses, including SFTSV, we find abundant virus-derived small interfering RNAs (vsiRNAs) are induced in H. longicornis after infection through either microinjection or natural blood-feeding. Furthermore, we identify a Dicer2-like homolog, the core protein of antiviral RNAi pathway, in H. longicornis and knocking down this gene exacerbated virus amplification. To counteract this antiviral RNAi of ticks, viruses have evolved suppressors of RNAi (VSRs). Here, we show that reduced viral replication inversely correlated with the accumulation of vsiRNAs in ticks after infection with recombinant sindbis virus (SINV) expressing heterologous VSR proteins. Elucidating the antiviral RNAi pathway of ticks by model arthropod-borne RNA viruses in vivo is critical to understanding the virus-host interaction, providing a feasible intervention strategy to control tick-borne arbovirus transmission.
Project description:Ticks are notorious carriers of pathogens; these blood-sucking arthropods can spread a variety of deadly diseases. The salivary gland is the main organ in ticks, and this organ begins to develop rapidly when Ixodidae ticks suck blood. When these ticks reach a critical weight, the salivary glands stop developing and begin to degenerate. Specific developmental features of the salivary glands are regulated by multiple factors, such as hormones, proteins and other small molecular substances. In this study, we used iTRAQ quantitative proteomics to study dynamic changes in salivary gland proteins in female Haemaphysalis longicornis at four feeding stages: unfed, partially fed, semi-engorged, and engorged. Through bioinformatics analysis of a large number of proteins, we found that molecular motor- and TCA cycle-related proteins play an important role during the development of the salivary glands. The results of RNAi experiments showed that when dynein, kinesin, isocitrate dehydrogenase, and citrate synthase were knocked down, ticks were unable to suck blood normally. The structure and function of the salivary glands were also significantly affected. In addition, four proteins from H. longicornis were found to have very low homology with those from mammals, including humans. Therefore, it is expected that drugs or antibodies targeting these unique sequences can be designed to kill ticks.