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Immunomodulation at the tick-virus-host interface during Powassan virus transmission
Paine, Dakota
Paine, Dakota
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2026-02-09
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DakotaPaineDissertation2026.pdf
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Powassan virus (POWV) is a neuroinvasive, tick-borne orthoflavivirus that circulates in the northeastern United States and parts of Canada. It is primarily transmitted to humans by Ixodes scapularis ticks at the skin interface during blood feeding, alongside a variety of pharmacologically active biomolecules found in tick saliva. Three major pillars characterize arboviral transmission: host, virus, and vector. The intersection of these pillars is crucial for understanding transmission and, consequently, human disease. To assess these pillars in a succinct and meaningful way, we designed a study based on initial POWV transmission to a host through Ixodes scapularis feeding. At the host level, we recently described the influential factors of POWV transmission at the bite site at a transcriptomic level using RNA sequencing technology. We found that during feeding, an inflammatory response is observed during the transmission of POWV to the host, compared to non-pathogen feedings. The transcriptomic data we acquired led us to investigate the NLRP3 inflammasome as a mediator of local inflammation during POWV infection. This study resulted in us establishing NLRP3 as a non-protective inflammasome during infection. Ticks are also critical to the transmission of POWV, so to investigate the role of tick salivary factors in POWV infection, we sequenced the salivary gland transcripts of POWV-infected Ixodes scapularis adults and generated a list of differentially expressed genes (DEGs) for analysis. After selecting candidate ii genes associated with transmission, we developed a pipeline to knock down target genes in the vector through dsRNA injection. We then assessed the transmission role of POWV from these dsRNA-treated ticks into mice. Through a combinatorial analysis of each pillar of arboviral disease, we have expanded our current understanding of the determinants of POWV transmission. Our next steps aim to evaluate the bioactivity of the identified molecules from Ixodes scapularis saliva at a mechanistic level to explore their role in pathogen transmission and vector-borne disease and apply these approaches to major vector-borne pathogens of human health concern.
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