Molecular Determinants of Flavivirus Virion Assembly

Virion assembly is an important step in the life cycle of all viruses. For viruses of the Flavivirus genus, a group of enveloped positive-sense RNA viruses, the assembly step represents one of the least understood processes in the viral life cycle. While assembly is primarily driven by the viral structural proteins, recent studies suggest that several nonstructural proteins also play key roles in coordinating the assembly and packaging of the viral genome. This review focuses on describing recent advances in our understanding of flavivirus virion assembly, including the intermolecular interactions between the viral structural (capsid) and nonstructural proteins (NS2A and NS2B-NS3), host factors, as well as features of the viral genomic RNA required for efficient flavivirus virion assembly. Flaviviruses, including Zika, dengue, and yellow fever viruses, annually impact millions of people.For infection to spread, virions must be packaged and assembled at the host endoplasmic reticulum (ER) membrane.Recent research provides insight into how flavivirus virions are assembled and how both viral structural and nonstructural (NS) proteins participate in this process.The α5 helix of the capsid protein, previously thought to be removed, may be partially retained on some capsid molecules and aids in capsid oligomerization for assembly.The viral NS2A protein appears to be a central hub in the packaging process, while the NS3 protein contributes to assembly through protease-mediated as well as nonenzymatic functions.