Membrane proteins organize a symmetrical virus

Alphaviruses are enveloped icosahedral viruses that mature by budding at the plasma membrane. According to a prevailing model maturation is driven by binding of membrane protein spikes to a preformed nucleocapsid (NC). The T = 4 geometry of the membrane is thought to be imposed by the NC through one‐to‐one interactions between spike protomers and capsid proteins (CPs). This model is challenged here by a Semliki Forest virus capsid gene mutant. Its CPs cannot assemble into NCs, or its intermediate structures, due to defective CP–CP interactions. Nevertheless, it can use its horizontal spike–spike interactions on membrane surface and vertical spike–CP interactions to make a particle with correct geometry and protein stoichiometry. Thus, our results highlight the direct role of membrane proteins in organizing the icosahedral conformation of alphaviruses.