New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated. Among the multiple active substances secreted during tick feeding, SPIs have been shown to be directly involved in regulation of inflammation, blood clotting, wound healing, vasoconstriction and the modulation of host defense mechanisms. In light of these activities, several SPIs were examined and were experimentally confirmed to facilitate tick pathogen transmission. In addition, to prevent coagulation of the ingested blood meal within the tick alimentary canal, SPIs are also involved in blood digestion and nutrient extraction from the meal. The presence of SPIs in tick hemocytes and their involvement in tick innate immune defenses have also been demonstrated, as well as their implication in hemolymph coagulation and egg development. Considering the involvement of SPIs in multiple crucial aspects of tick-host-pathogen interactions, as well as in various aspects of the tick parasitic lifestyle, these molecules represent highly suitable and attractive targets for the development of effective tick control strategies. Here we review the current knowledge regarding this class of inhibitors in tick biology and tick-borne pathogen transmission, and their potential as targets for future tick control trials.

More than 25% of human infectious diseases are vector-borne diseases (VBDs). These diseases, caused by pathogens shared between animals and humans, are a growing threat to global health with more than 2.5 million annual deaths. Mosquitoes and ticks are the main vectors of arboviruses including flaviviruses, which greatly affect humans. However, all tick or mosquito species are not able to transmit all viruses, suggesting important molecular mechanisms regulating viral infection, dissemination, and transmission by vectors. Despite the large distribution of arthropods (mosquitoes and ticks) and arboviruses, only a few pairings of arthropods (family, genus, and population) and viruses (family, genus, and genotype) successfully transmit. Here, we review the factors that might limit pathogen transmission: internal (vector genetics, immune responses, microbiome including insect-specific viruses, and coinfections) and external, either biotic (adult and larvae nutrition) or abiotic (temperature, chemicals, and altitude). This review will demonstrate the dynamic nature and complexity of virus–vector interactions to help in designing appropriate practices in surveillance and prevention to reduce VBD threats.