NECing goes: flexibility of the herpesvirus nuclear egress complex

Abstract The nuclear egress complex (NEC) allows herpesvirus capsids to escape from the nucleus without breaking the nuclear envelope barrier. It assembles into a lattice on the inner nuclear membrane enveloping newly assembled nucleocapsids, which bud into the perinuclear space. The primary virion envelope subsequently fuses with the outer nuclear membrane, releasing the capsid into the cytosol. Here we interrogated the NEC in the context of intact cells infected with pseudorabies or herpes simplex virus using focused-ion beam milling and electron cryo- tomography. We determined the structure of NEC in different conformations and show that it consists of a flexible hexameric lattice that generates curvature through a combination of ordered and disordered domains. After interrogating the intermediate stages of capsid formation, we show that capsid vertex binding may initiate envelopment but does not directly induce curvature formation. These data and many examples of the intermediate stages of nuclear egress paint a detailed holistic view of a versatile transport system.