Project description:Powassan virus (POWV) causes highly lethal encephalitis in the elderly and long-term cognitive deficits in survivors. Mirroring human severity, POWV LI9 directs age-dependent lethality in B6 mice resulting in spongiform encephalitis, gliosis and inflammatory cytokine/chemokine responses in the CNS. Here we analyzed POWV LI9 infected brains from 10 (young) and 50 week old (aged) B6 mice using 10x Genomics scRNA-seq to define CNS responses that direct age-dependent lethality.

2026-05-28 | GSE329199 | GEO

Restraint of Powassan virus replication by TRIM5a facilitates viral avoidance of antiviral immunity

Project description:TRIpartite Motif (TRIM) protein 5 alpha (TRIM5a) is a well characterized cellular inhibitor of lentivirus replication that limits transmission of related viruses between primates. We previously reported that TRIM5a derived from humans and rhesus macaques inhibits replication of orthoflaviviruses belonging to the tick-borne encephalitis virus (TBEV) serocomplex, including TBEV, Kyasanur forest disease virus and Langat virus (LGTV), but interestingly not the tick-borne Powassan virus (POWV). To further characterize the primate TRIM5a and orthoflavivirus interface, we screened TRIM5a variants from representative old- and new-world primates for restriction capacity. TRIM5a from old-world African green monkey, De Brazza’s monkey and chimpanzee demonstrated virus-specific restriction of tick-borne orthoflaviviruses. Efforts to determine why TRIM5a fails to inhibit POWV revealed that our lab stock had acquired a non-synonymous mutation in NS3 that, when introduced into a POWV molecular clone, facilitated virus replication in the presence of all inhibitory primate TRIM5a proteins. Infection of human dendritic cells with TRIM5a-resistant POWV resulted in high early replication and strong induction of interferon responses that limited replication compared with the wild-type virus. Thus, primate TRIM5a functions as a potent cellular barrier to infection with tick-borne orthoflaviviruses that restrains replication to a level that may help avoid early innate immune recognition.

2026-06-17 | GSE325334 | GEO

Early transcriptomic changes at the skin interface during Powassan virus transmission by Ixodes scapularis ticks

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.

2025-02-05 | GSE282786 | GEO

Age-dependent CNS responses to Powassan virus infection revealed by single-cell RNA sequencing

Project description:Age-dependent CNS responses to Powassan virus infection revealed by single-cell RNA sequencing

| PRJNA1458141 | ENA

Early transcriptomic changes at the skin interface during Powassan virus transmission by Ixodes scapularis ticks

Project description:Early transcriptomic changes at the skin interface during Powassan virus transmission by Ixodes scapularis ticks

| PRJNA1190418 | ENA