Escaping the nucleus: the herpesvirus struggle

Following assembly, herpesvirus capsids exit the nucleus by budding at the nuclear membrane. This process is mediated by the nuclear egress complex (NEC), a heterodimer of the viral proteins pUL31 and pUL34 that forms a hexagonal lattice at the inner nuclear membrane. Despite the accumulation of immature and defective capsids that do not contain DNA genomes in the nucleus, only mature genome-filled capsids efficiently egress to the cytosol. The interactions between capsids and the NEC are poorly understood, as is the mechanism underlying capsid selectivity. In this study we describe a new approach to tagging capsids with a fluorescent protein that allows for visualization of both immature and mature capsids. Using this reporter virus, the dynamics of capsid localization and maturation were examined within the nuclei of living and fixed cells. We find that capsid docking at the inner nuclear membrane requires capsid maturation, while budding is dependent upon genome encapsidation.