Human hair-bearing skin organoids reveal cell type-specific susceptibility and innate immune responses to herpes simplex virus 1.

Human hair-bearing skin organoids show cell type-specific HSV-1 susceptibility and spatially organized innate responses, including IER3 induction in papillary fibroblasts and IRF3 up-regulation in basal keratinocytes.

• Why it matters: Epithelial HSV-1 infection depends on skin architecture, but how viral spread and antiviral or inflammatory signaling vary by cell type and location is not well mapped in human tissue models.
• What they did: The study infected human hair-bearing skin organoids and used single-cell spatial transcriptomics plus imaging to track viral spread and host gene expression across epidermis, dermis, and hair follicles, validating cytokines by ELISA.
• The result: Interferon-β reduced viral replication, while TNF-α and 4-1BBL did not; TNF-α–linked chemokines CXCL2 and CXCL10 were secreted and CXCL2 was enriched near TNF-α–expressing cells, supporting spatial immune orchestration.

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