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Dahmane S, Schexnaydre E, Zhang J, Rosendal E, Chotiwan N, Singh BK, Yau WL, Lundmark R, Barad B, Grotjahn DA, Liese S, Carlson A, Överby AK, Carlson LA
bioRxiv - (-) - [2024-10-21; online 2024-10-21]
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.
PubMed 39416041
DOI 10.1101/2024.10.13.618056
Crossref 10.1101/2024.10.13.618056
pmc: PMC11482891
pii: 2024.10.13.618056