Capsid protein is central to the birth of flavivirus particles

Abstract

Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) are enveloped, positivesense single-stranded RNA viruses. Upon entry into a host cell by receptor-mediated endocytosis, the virus particle undergoes low-pH-driven endosomal membrane fusion to release its genome into the cytoplasm This viral genome is then translated into a single polyprotein that is co-and post-translationally processed into 3 structural and 7 nonstructural proteins. The 3 structural proteins that form the immature virus particle are the Capsid (C), Envelope (E), and precursor Membrane (prM) proteins. After formation of the core, consisting of the C protein complexed with the newly synthesized viral RNA genome, the core then buds into the endoplasmic reticulum (ER) membrane decorated with membrane-anchored viral E and prM proteins, forming an immature virus (Fig The immature virion then undergoes maturation during transport through the secretory pathway (Fig 1B). This involves large conformational rearrangements of the E proteins (Fig 2A), which enhances the cleavage of the prM to M protein by furin proteases (Fig 1C) to generate the infectious mature virus particle (Fig 1D).

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