2026-07-14 ロックフェラー大学
＜関連情報＞
- https://www.rockefeller.edu/news/40073-virus-brain-wnv-encephalitis/
- https://www.cell.com/immunity/fulltext/S1074-7613(26)00260-8
脳内皮細胞は、末梢のウイルスパターン認識に応答して、中枢神経系において神経保護的な抗ウイルス状態を調整する Brain endothelial cells orchestrate a neuroprotective antiviral state in the CNS in response to peripheral viral pattern sensing
Tyler Lewy ∙ Maria A. Sierra, ∙ Nastaran Pourshadi ∙ … ∙ James E. Crowe, Jr. ∙ Charles M. Rice ∙ Alexander Lercher
Immunity Published:July 2, 2026
DOI:https://doi.org/10.1016/j.immuni.2026.06.009
Highlights
- Peripheral viral pattern sensing primes antiviral defenses in the CNS
- Serum IFN-α is necessary and sufficient for the establishment of this antiviral state
- Brain endothelial cells of the CNS are the primary responders to systemic IFN-α
- IFNAR1 signaling in brain endothelial cells is necessary for neuroprotection
Summary
West Nile virus (WNV) and other neurotrophic arboviruses are human pathogens that can cause life-threatening encephalitis. To uncover determinants of severe disease progression, we employed a murine infection model of WNV and experimentally uncoupled peripheral pathogen sensing from active viral replication. Peripheral sensing of a viral dsRNA mimic in the footpad led to robust induction of antiviral type I interferon (IFN-I)-stimulated genes and establishment of an antiviral state within the brain. Systematic approaches combining cytokine profiling, single-nuclei transcriptomics, immune modulation, and genetic perturbations revealed critical roles for systemic IFN-I and IFN-I receptor signaling in brain microvascular endothelial cells. This inter-organ antiviral crosstalk protected against severe encephalitis caused by a range of neurotropic viruses across Orthoflaviviridae, Togaviridae, and Orthoherpesviridae. Thus, these data unravel a cross-tissue antiviral signaling network that counteracts lethal encephalitis, pointing to therapeutic avenues for encephalitic disease caused by emerging viral pathogens.
