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Cryo-electron tomography reveals coupled flavivirus replication, budding and maturation
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).ORCID iD: 0000-0003-4193-1496
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.ORCID iD: 0000-0002-2993-8647
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
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2026 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 17, no 1, article id 828Article in journal (Refereed) Published
Abstract [en]

Flaviviruses replicate their genomes in replication organelles (ROs) formed as bud-like invaginations on the endoplasmic reticulum membrane, which also functions as the site for virion assembly. While this localization is well established, it is not known to what extent viral membrane remodeling, genome replication, virion assembly, and maturation are coordinated. Here, we image tick-borne flavivirus replication in human cells using cryo-electron tomography. We find that the RO membrane bud is shaped by a combination of a curvature-establishing membrane modification and the pressure from intraluminal template RNA. A protein complex at the RO base extends to an adjacent membrane, where immature virus particles bud. Naturally occurring furin site variants determine whether virus particles mature in the immediate vicinity of ROs. We further visualize replication in mouse brain tissue by cryo-electron tomography. Taken together, these findings reveal a close spatial coupling of flavivirus genome replication, budding, and maturation.

Place, publisher, year, edition, pages
Springer Nature, 2026. Vol. 17, no 1, article id 828
National Category
Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-249440DOI: 10.1038/s41467-026-68483-4ISI: 001667080400002PubMedID: 41559045Scopus ID: 2-s2.0-105028335488OAI: oai:DiVA.org:umu-249440DiVA, id: diva2:2037336
Funder
Swedish Research Council, 2021–01145Swedish Research Council, 2023-02664Swedish Research Council, 2024-00390Swedish Research Council, 2018–05851Swedish Research Council, 2020-06224The Kempe Foundations, SMK-1654The Kempe Foundations, JCK-1827Knut and Alice Wallenberg Foundation, 2024.0039Available from: 2026-02-10 Created: 2026-02-10 Last updated: 2026-02-10Bibliographically approved

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Dahmane, SelmaSchexnaydre, ErinZhang, JianguoSingh, Bina K.Rosendal, EbbaChotiwan, NunyaNilsson, EmmaPeters, Marie Berit AkpiroroYau, Wai-LokRönfeldt, SebastianLundmark, RichardCarlson, AndreasÖverby, Anna K.Carlson, Lars-Anders

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Dahmane, SelmaSchexnaydre, ErinZhang, JianguoSingh, Bina K.Rosendal, EbbaChotiwan, NunyaNilsson, EmmaPeters, Marie Berit AkpiroroYau, Wai-LokRönfeldt, SebastianLundmark, RichardCarlson, AndreasÖverby, Anna K.Carlson, Lars-Anders
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Department of Medical Biochemistry and BiophysicsWallenberg Centre for Molecular Medicine at Umeå University (WCMM)Molecular Infection Medicine Sweden (MIMS)Umeå Centre for Microbial Research (UCMR)Department of Clinical MicrobiologyDepartment of ChemistryDepartment of Medical and Translational Biology
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Nature Communications
Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

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