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TitleCryo-electron tomography reveals coupled flavivirus replication, budding and maturation.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateOct 21, 2024
AuthorsSelma Dahmane / Erin Schexnaydre / Jianguo Zhang / Ebba Rosendal / Nunya Chotiwan / Bina Kumari Singh / Wai-Lok Yau / Richard Lundmark / Benjamin Barad / Danielle A Grotjahn / Susanne Liese / Andreas Carlson / Anna Overby / Lars-Anders Carlson
PubMed AbstractFlaviviruses replicate their genomes in replication organelles (ROs) formed as bud-like invaginations on the endoplasmic reticulum (ER) membrane, which also functions as the site for virion assembly. ...Flaviviruses replicate their genomes in replication organelles (ROs) formed as bud-like invaginations on the endoplasmic reticulum (ER) 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 imaged 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 coat and the pressure from intraluminal template RNA. A protein complex at the RO base extends to an adjacent membrane, where immature virions bud. Naturally occurring furin site variants determine whether virions 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.
External linksbioRxiv / PubMed:39416041 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution33.0 - 80.0 Å
Structure data

EMDB-51640: Subtomogram average of immature Langat virus from cryo-electron tomograms of infected cells
Method: EM (subtomogram averaging) / Resolution: 33.0 Å

EMDB-51642: Subtomogram average of mature Langat virus
Method: EM (subtomogram averaging) / Resolution: 80.0 Å

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