02723nas a2200421   4500000000100000000000100001008004100002260001500043653002600058653001400084653002300098100002700121700001500148700002000163700002100183700001700204700001800221700003300239700002500272700002100297700001800318700002200336700001700358700001900375700001900394700001700413700002200430700002200452700001900474700001500493700001900508245010000527856005500627300000900682490000700691520158900698022001402287       2025                            d  c2025-06-3010aMechanisms of disease10aPox virus10aViral pathogenesis1 aIsabel Schultz-Pernice1 aAmal Fahmi1 aFrancisco Brito1 aMatthias Liniger1 aYen-Chi Chiu1 aTeodora David1 aBlandina I. Oliveira Esteves1 aAntoinette Golomingi1 aBeatrice Zumkehr1 aMarkus Gerber1 aDamian Jandrasits1 aRoland Züst1 aSelina Steiner1 aCarlos Wotzkow1 aFabian Blank1 aOlivier B. Engler1 aArtur Summerfield1 aNicolas Ruggli1 aDavid Baud1 aMarco P. Alves00aMonkeypox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids  uhttps://www.nature.com/articles/s41467-025-61134-0  a53760 v163 aIn 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. Here, we analyze the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate. We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons. The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories. Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus, suggesting viral cell-to-cell spread. Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission. We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative disorders. Bead appearance precedes neurite-initiated cell death, as confirmed through live-cell imaging. Accordingly, hNO-transcriptome analysis reveals alterations in cellular homeostasis and upregulation of neurodegeneration-associated transcripts, despite scarcity of inflammatory and antiviral responses. Notably, tecovirimat treatment of MPXV-infected hNOs significantly reduces infectious virus loads. Our findings suggest that viral disruption of neuritic transport drives neuronal degeneration, potentially contributing to MPXV neuropathology and revealing targets for therapeutic intervention.  a2041-1723