01696nas a2200217   4500000000100000000000100001008004100002260001500043653002000058653002000078100003100098700002000129700002100149700001700170245009800187856005500285300000900340490000700349520110800356022001401464       2026                            d  c2026-03-0710aInnate immunity10aWest nile virus1 aJohanna Friederike Steffen1 aLina Widerspick1 aStephanie Jansen1 aDennis Tappe00aA human cerebral organoid model of West Nile virus encephalitis shows innate immunocompetency  uhttps://www.nature.com/articles/s41467-026-70281-x  a23180 v173 aWest Nile virus (WNV), an arbovirus of emerging global interest, can cause neuroinvasive disease in humans. Currently, no protective vaccine or specific treatment is available for human WNV encephalitis. The virus induces neuronal cell death, while astrocytes and microglia cells are suspected to contribute to WNV pathology. Hence, understanding their role is crucial for future treatment approaches. In this study, we establish a WNV encephalitis model using human cerebral organoids, generated with male iPSCs. Infection results in heterogeneous kinetics with an early strong replication potentially leading to viral clearance, while a late peak was associated with more long-term infection. Viral foci are seen in cortical-like areas, rich in neurons and astrocytes, however void of microglia. Pro-inflammatory cytokines (IL-6, TNF-α, IL-18), chemokines (CXCL10, CCL17, CX3CL1, CCL2) and biomarkers (IL-1RA, sTREM-1, sRAGE, BDNF) are increasingly released. Conclusively, human cerebral organoids make suitable WNV encephalitis models with valuable properties to study acute and long-term infection.  a2041-1723