The replication cycle of alphaviruses. The virion enters a susceptible cell via receptor mediated endocytosis, primarily mediated by clathrin (green) and due to pH changes of the endosome releases its RNA (purple) into the cytoplasm of the host cell. The positive sense genomic RNA is first used by ribosomes to translate the viral nsPs as a polyprotein (yellow = nsP123, green = nsP4). The polyprotein will undergo cleavage events that control the synthesis of the viral RNA species (individual nsPs represented as single green circles). This RNA synthesis occurs in membrane invaginations that are termed spherules. These spherules protect the viral RNA and nsPs from detection by the host cell. Late in infection the structural genes are synthesized (pink = the E proteins, black = capsid). The capsid will form into nucleocapsid cores as it packages the viral RNA, and the glycoproteins are transported to the cell membrane. The nucleocapsid cores translocate to the cellular membrane where they bud off, collecting their envelope and glycoproteins and forming new infectious virions.