Functions of alphavirus nonstructural proteins in RNA replication

Alphaviruses are enveloped positive-strand RNA viruses transmitted to vertebrate hosts by mosquitoes. Several alphaviruses are pathogenic to humans or domestic animals, causing serious central nervous system infections or milder infections, for example, arthritis, rash, and fever. The structure and replication of Semliki Forest virus (SFV) and Sindbis virus (SIN) have been studied extensively during the past 30 years. Alphaviruses have been important probes in cell biology to study the translation, glycosylation, folding, and transport of membrane glycoproteins, as well as endocytosis and membrane fusion mechanisms. A new organelle, the intermediate compartment, operating between the endoplasmic retieulum and the Golgi complex has been found by the aid of SFV. During the past 10 years, alphavirus replicons have been increasingly used as expression vectors for basic research, for the generation of vaccines, and for the production of recombinant proteins in industrial scale. The main approaches of laboratories in the recent years have been twofold. On one hand, they have discovered and characterized the enzymatic activities of the individual replicase proteins and on the other hand, they have studied the localization, membrane association, and other cell biological aspects of the replication complex.