Abstract

Chikungunya virus is a single-stranded RNA virus that infects mammals and birds and is transmitted by an invertebrate vector. This virus belongs to the Alphavirus genus and is structurally characterized by two concentric T = 4 icosahedral shells separated by a lipid bilayer. Initially, it was thought that in the cytoplasm, the core (inner shell) was icosahedral; however, recent data using Cryo-ET has shown that in the cytoplasm, the core is amorphous, and it is only upon interacting with the glycoproteins (E1 and E2) that are in the plasma membrane that the double icosahedron is assembled during budding. Additionally, it was believed that the primary driving force behind assembly and budding was the interaction between the core and the glycoprotein E2. However, our experimental and coarse-grained simulation data strongly suggest that other protein-protein interactions are required for correct assembly, efficient budding, and particle stability. In particular, we show that a steric repulsion between trimers of the heterodimers of E1/E2 is required for assembly and particle stability. Furthermore, we show that removing this steric interaction affects particle morphology, suggesting that these sugars act as a molecular handshake.