Cryo-electron tomography reveals coupled flavivirus replication, budding and maturationVisa övriga samt affilieringar
2026 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 17, nr 1, artikel-id 828Artikel i tidskrift (Refereegranskat) 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.
Ort, förlag, år, upplaga, sidor
Springer Nature, 2026. Vol. 17, nr 1, artikel-id 828
Nationell ämneskategori
Medicinsk bioteknologi (Inriktn. mot cellbiologi (inkl. stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
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
Forskningsfinansiär
Vetenskapsrådet, 2021–01145Vetenskapsrådet, 2023-02664Vetenskapsrådet, 2024-00390Vetenskapsrådet, 2018–05851Vetenskapsrådet, 2020-06224Kempestiftelserna, SMK-1654Kempestiftelserna, JCK-1827Knut och Alice Wallenbergs Stiftelse, 2024.00392026-02-102026-02-102026-02-10Bibliografiskt granskad