Intranasal HSV‑1 infection drives region‑specific interferon‑dominant microglial remodeling.

Intranasal HSV‑1 infection causes region-specific microglial remodeling dominated by interferon-driven regulatory programs in the CNS.

• Why it matters: Understanding how microglia respond to HSV‑1 infection is crucial because it may reveal mechanisms underlying chronic neuroinflammation and neurodegenerative disease risk associated with viral infections.
• What they did: The study used integrated single-nucleus RNA sequencing, chromatin accessibility profiling, and spatial proteomics and transcriptomics in an intranasal HSV‑1 infection model, analyzing over 10,000 nuclei to identify distinct microglial and macrophage populations and their spatial distribution.
• The result: HSV‑1 infection induces localized transcriptional and epigenetic changes in microglia characterized by increased interferon responses and decreased homeostatic signatures, providing mechanistic insights into sustained neuroinflammation and long-term neurological vulnerability.