Inefficient tissue immune response against MPXV in an immunocompromised mpox patient

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dc.citation.articleNumbere29811en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitleJournal of Medical Virologyen_US
dc.citation.volumeNumber96en_US
dc.contributor.authorMatschke, Jakoben_US
dc.contributor.authorHartmann, Kristinen_US
dc.contributor.authorPfefferle, Susanneen_US
dc.contributor.authorWang, Yueen_US
dc.contributor.authorValdes, Pablo A.en_US
dc.contributor.authorThies, Eddaen_US
dc.contributor.authorSchweizer, Michaelaen_US
dc.contributor.authorLütgehetmann, Marcen_US
dc.contributor.authorSchmiedel, Stefanen_US
dc.contributor.authorBernreuther, Christianen_US
dc.contributor.authorBoyden, Edward S.en_US
dc.contributor.authorGlatzel, Markusen_US
dc.contributor.authorKrasemann, Susanneen_US
dc.date.accessioned2024-08-09T16:25:24Zen_US
dc.date.available2024-08-09T16:25:24Zen_US
dc.date.issued2024en_US
dc.description.abstractThe recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV and low CD4 T cell counts might develop a fulminant clinical mpox course with increased mortality, secondary infections, and necrotizing lesions. Fatal cases display a high and widespread MPXV tissue burden. The underlying pathomechanisms are not fully understood. We report here the pathological findings of an MPXV-driven abscess in gastrocnemius muscle requiring surgery in an immunocompromised patient with severe mpox. Presence of virus particles and infectivity were confirmed by electron microscopy, expansion microscopy, and virus culture, respectively. MPXV tissue distribution by immunohistochemistry (IHC) showed a necrotic core with infection of different cell types. In contrast, at the lesion rim fibroblasts were mainly infected. Immune cells were almost absent in the necrotic core, but were abundant at the infection rim and predominantly macrophages. Further, we detected high amounts of alternatively activated GPNMB+-macrophages at the lesion border. Of note, macrophages only rarely colocalized with virus-infected cells. Insufficient clearance of infected cells and infection of lesion-associated fibroblasts sustained by the abundance of profibrotic macrophages might lead to the coalescing of lesions and the severe and persistent clinical mpox course observed in immunocompromised patients.en_US
dc.identifier.citationMatschke, J., Hartmann, K., Pfefferle, S., Wang, Y., Valdes, P. A., Thies, E., Schweizer, M., Lütgehetmann, M., Schmiedel, S., Bernreuther, C., Boyden, E. S., Glatzel, M., & Krasemann, S. (2024). Inefficient tissue immune response against MPXV in an immunocompromised mpox patient. Journal of Medical Virology, 96(7), e29811. https://doi.org/10.1002/jmv.29811en_US
dc.identifier.digitalInefficient-tissueen_US
dc.identifier.doihttps://doi.org/10.1002/jmv.29811en_US
dc.identifier.urihttps://hdl.handle.net/1911/117622en_US
dc.language.isoengen_US
dc.publisherWileyen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial (CC BY-NC) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.titleInefficient tissue immune response against MPXV in an immunocompromised mpox patienten_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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