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Abstract
Ticks are hematophagous arthropods that transmit a number of pathogens while feeding. Among these is tick-borne encephalitis virus (TBEV), a flavivirus transmitted by Ixodes ricinus ticks in the temperate zone of Europe. The infection results in febrile illness progressing to encephalitis and meningitis with a possibility of fatality or long-term neurological sequelae. The composition of tick saliva plays an essential role in the initial virus transmission during tick feeding. Ticks secrete a diverse range of salivary proteins to modulate the host response, such as lipocalins to control the itch and inflammatory response, and both proteases and protease inhibitors to prevent blood coagulation. Here, the effect of viral infection of adult females of Ixodes ricinus was studied with the goal of determining how the virus alters the tick sialome to modulate host tissue response at the site of infection. Uninfected ticks or those infected with TBEV were fed on mice and removed and dissected one- and 3-h post-attachment. RNA from the salivary glands of these ticks, as well as from unfed ticks, was extracted and subjected to next-generation sequencing to determine the expression of key secreted proteins at each timepoint. Genes showing statistically significant up- or down-regulation between infected and control ticks were selected and compared to published literature to ascertain their function. From this, the effect of tick viral infection on the modulation of the tick-host interface was determined. Infected ticks were found to differentially express a number of uncategorized genes, proteases, Kunitz-type serine protease inhibitors, cytotoxins, and lipocalins at different timepoints. These virus-induced changes to the tick sialome may play a significant role in facilitating virus transmission during the early stages of tick feeding.
Highlights
Ticks are obligate hematophagous arthropods of the order Ixodida that transmit a variety of disease agents to humans and animals
To understand the differential response of the I. ricinus salivary gland transcriptome during early stages of tick-borne encephalitis virus (TBEV) transmission, ticks were inoculated with TBEV by coxal microinjection 21 days prior to being fed on mice
This technique for infection is allowed for the generation of infected ticks with a high rate of success and has been widely accepted
Summary
Ticks are obligate hematophagous arthropods of the order Ixodida that transmit a variety of disease agents to humans and animals. In Europe, Russia, and Northern Asia, tick-borne viral diseases are a major public health concern. Of particular concern is tick-borne encephalitis virus (TBEV), a flavivirus endemic to Europe and northern Asia which is vectored by Ixodes ricinus in Europe and Ixodes persulcatus in parts of Eastern Europe and Asiatic Russia. The virus is transported by these macrophages to the draining lymph nodes, where it replicates before entering the blood and progressing to the remainder of the body. This results in febrile illness that may progress to neuroinvasive disease with meningitis or in more severe cases to encephalitis or myeloencephalitis (Zavadska et al, 2018). The fatality rate of the European subtype of TBE (transmitted by I. ricinus) is 1–3%, with over 40% of neuroinvasive cases resulting in long-term neurological sequelae
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