Flavivirus structure and membrane fusion

Flaviviruses are spherical enveloped viruses with a diameter of approximately 50 nm that contain only three structural proteins: E (envelope), prM/M (membrane), and C (capsid). This chapter focuses primarily on structural aspects of the envelope glycoproteins, their organization in the viral envelope, and the mechanism of virus-induced membrane fusion. Significant progress has been made toward the understanding of the structure and organization of the flavivirus virion. The current view of the flavivirus life cycle, including entry, assembly, maturation, and release suggests that virus entry occurs by receptor-mediated endocytosis, and the acidic pH in the endosome triggers structural alterations in the E protein that lead to the fusion of the viral membrane with the endosomal membrane and the release of the nucleocapsid. During assembly, immature prM-containing virions are believed to be formed in the endoplasmic reticulum (ER) and transported through the secretory pathway of the cell. The most important structural features revealed by current studies are: an icosahedral arrangement of the envelope proteins and a characteristic envelope protein structure, which, together with the alphavirus E1 protein, defines a separate class of viral fusion protein.