A large fraction of mosquito-borne viruses that infect humans rely on a peculiar reshaping of cellular membranes in the infected cells. This reshaping of the cell’s membranes into a ~100 nm large bud is a crucial step in forming what is called a “replication organelle”, which is the factory that mass-produces the virus genes for packaging into new virus particles.
We study the formation, structure and function of replication organelles using a microscopy method called cryo-electron tomography. This is the only method that allows 3D visualisation of the unperturbed interior of the cell at nanometre resolution. The 3D closeups of these phenomena allow powerful discoveries to be made by “just looking at the thing” (to quote Richard Feynman) but are even more powerful when combined with e.g. mathematical models of membrane remodelling. Here, we present our cryo-electron tomography studies of replication organelles from two mosquito-borne virus types - alphaviruses and flaviviruses - with a focus on their macromolecular architecture and biophysical principles of their formation. Interestingly, the replication organelles of these two virus types produce a near-identical remodelling of cellular membranes into a bud, even though they use different cellular membranes and different molecular mechanisms to conduct the membrane remodelling.