# Ixodes scapularis STING promotes Powassan virus infection in ticks

## TL;DR

A tick protein called tSTING helps Powassan virus infect ticks, unlike its human counterpart that fights viruses.

## Contribution

The study reveals that tick STING promotes rather than inhibits viral infection, contrasting with mammalian STING.

## Key findings

- tSTING regulates glycosylation and endocytosis, which are crucial for Powassan virus entry in ticks.
- Silencing a glycosylation enzyme reduced viral loads, linking tSTING to viral uptake.
- Human STING restricts the virus through a different mechanism involving OAS1, independent of glycosylation.

## Abstract

The stimulator of interferon genes (STING) is a central adaptor in antiviral signaling, but its role in vectors that transmit human and animal pathogens remains poorly understood. Here, we show that the tick STING homolog, tSTING, facilitates Powassan virus (POWV) infection in Ixodes scapularis -- in contrast to the canonical antiviral activity of mammalian STING. Transcriptomic and functional analyses revealed that tSTING regulates N-linked glycosylation and endocytosis, pathways essential for viral entry. Silencing of RPN2, a key glycosylation enzyme, significantly reduced viral loads, establishing a mechanistic link between tSTING and glycosylation-mediated viral uptake. Moreover, parallel studies in human THP-1 cells suggest human STING (hSTING) displays an opposite phenotype, restricting POWV replication potentially through OAS1-associated antiviral mechanisms independent of glycosylation. Together, these findings reveal an evolutionary reversal of STING function between arthropods and mammals, redefining the evolutionary logic of antiviral immunity across vector–host boundaries.