Cryo-electron tomography reveals coupled flavivirus replication, budding and maturation
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.
Authors
- Lars A. Carlson (ORCID: https://orcid.org/0000-0003-2342-6488)
- Erin Schexnaydre (ORCID: https://orcid.org/0000-0002-2993-8647)
- Richard Lundmark (ORCID: https://orcid.org/0000-0001-9104-724X)
- Susanne Liese (ORCID: https://orcid.org/0000-0001-7420-5488)
- Selma Dahmane (ORCID: https://orcid.org/0000-0003-4193-1496)
- Nunya Chotiwan (ORCID: https://orcid.org/0000-0003-3214-6605)
- Anna K. Överby (ORCID: https://orcid.org/0000-0001-6553-0940)
- Danielle Ann Grotjahn (ORCID: https://orcid.org/0000-0001-5908-7882)
- Benjamin A. Barad (ORCID: https://orcid.org/0000-0002-1016-862X)
- Kiran Bala Sharma (ORCID: https://orcid.org/0000-0002-2575-4525)
- Ebba Rosendal (ORCID: https://orcid.org/0000-0001-8512-0535)
- Bina Kumari Singh (ORCID: https://orcid.org/0000-0002-9500-2759)
- Sebastian Rönfeldt (ORCID: https://orcid.org/0009-0005-6207-3162)
- Wai-Lok Yau
- Marie B. A. Peters
- Andreas Carlson
- Jianguo Zhang
- Emma Nilsson
Institutions
- Scripps Research Institute (US)
- Oregon Health & Science University (US)
- University of Augsburg (DE)
- University of Oslo (NO)
- Mahidol University (TH)
- Rosalind Franklin Institute (GB)
- Friedrich Miescher Institute (CH)
- Ramathibodi Hospital (TH)
- Umeå University (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-01-20
- DOI
- https://doi.org/10.1038/s41467-026-68483-4
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00