Project description:Powassan virus (POWV), a vector-borne pathogen transmitted by Ixodes ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick-feeding and salivary factors modulate the host's immunological responses, facilitating blood feeding and pathogen transmission. However, the mechanisms of immunomodulation during POWV transmission remain inadequately understood. In this study, we investigated the global cutaneous transcriptomic changes associated with tick bites during POWV transmission. We collected skin biopsies from the tick attachment sites at 1-, 3-, and 6-hours post-feeding by POWV-infected and uninfected ticks, followed by RNA sequencing of these samples. Differentially expressed genes were analyzed for pathway enrichment using gene ontology and pathway enrichment analyses. Our findings reveal that tick feeding alone significantly impacts the skin transcriptome within the first 1 to 3 hours of tick attachment. Although early POWV transmission induces minimal changes in the local environment, a pronounced shift toward a proinflammatory state is observed 6 hours post tick attachment, characterized by neutrophil recruitment and interleukin signaling. These transcriptomic data elucidate the dynamic changes at the tick bite site, transitioning from changes that assist blood meal acquisition to a proinflammatory phase that may facilitate viral dissemination.
Project description:BackgroundPowassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes.MethodsA retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases.ResultsSixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%).ConclusionsTo our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease.
Project description:Powassan virus (POW) is a tick-borne flavivirus distributed in Canada, the northern USA and the Primorsky region of Russia. POW is the only tick-borne flavivirus endemic to the western hemisphere, where it is transmitted mainly between Ixodes cookei and groundhogs (Marmota monax). Deer tick virus (DTV), a genotype of POW that has been frequently isolated from deer ticks (Ixodes scapularis), appears to be maintained in an enzootic cycle between these ticks and white-footed mice (Peromyscus leucopus). DTV has been isolated from ticks in several regions of North America, including the upper Midwest and the eastern seaboard. The incidence of human disease due to POW is apparently increasing. Previous analysis of tick-borne flaviviruses endemic to North America have been limited to relatively short genome fragments. We therefore assessed the evolutionary dynamics of POW using newly generated complete and partial genome sequences. Maximum-likelihood and Bayesian phylogenetic inferences showed two well-supported, reciprocally monophyletic lineages corresponding to POW and DTV. Bayesian skyline plots based on year-of-sampling data indicated no significant population size change for either virus lineage. Statistical model-based selection analyses showed evidence of purifying selection in both lineages. Positive selection was detected in NS-5 sequences for both lineages and envelope sequences for POW. Our findings confirm that POW and DTV sequences are relatively stable over time, which suggests strong evolutionary constraint, and support field observations that suggest that tick-borne flavivirus populations are extremely stable in enzootic foci.