Intracytoplasmic vesicular transport is well established; nucleo-cytoplasmic transport has so far been thought to be restricted to passage through the nuclear pore either passively, if size permits, or via karyopherin-mediated active transport. This limits transport in and out of the nucleus to particles of a maximum of 39 nm. With a diameter of 120 nm, herpesvirus capsids, which are assembled in the nucleus but mature to infectious virions in the cytosol, are unable to pass through the nuclear pore. It has become clear in the last decade that they leave the nucleus and traverse the nuclear envelope by a vesicle-mediated process that entails budding of nucleocapsids at the inner nuclear membrane, forming a primary enveloped virion in the perinuclear space. The primary envelope then fuses with the outer nuclear membrane.
Long thought to be specific for herpesviruses, this pathway has recently also been suggested to function in the export of large ribonucleoprotein (RNP) complexes during development of Drosophila. Common between the two is the involvement of kinases (viral, cellular, or both) to phosphorylate and soften the nuclear lamina allowing access of the ‘cargo’ (i.e., viral nucleocapsids or cellular RNPs) to the INM as well as morphological similarities . The cellular AAA+ ATPase TorsinA has also been proposed to be involved in both processes. Thus the notion was developed that herpesviruses have actually co-opted a hitherto cryptic cellular transport pathway for their replication.
Vesicular Nucleo-Cytoplasmic Transport – Herpesviruses as Pioneers in Cell Biology. Viruses 2016, 8 (10): 266. doi:10.3390/v8100266
Herpesviruses use a vesicle-mediated transfer of nuclear-assembled nucleocapsids through the nuclear envelope for maturation in the cytoplasm. The molecular basis for this novel vesicular nucleo-cytoplasmic transport is beginning to be elucidated in detail. The heterodimeric viral nuclear egress complex, conserved within the classical herpesviruses, mediates vesicle formation from the inner nuclear membrane by polymerization into a hexagonal lattice followed by fusion of the vesicle membrane with the outer nuclear membrane. Mechanisms of capsid inclusion as well as vesicle-membrane fusion, however, are largely unclear. Interestingly, a similar transport mechanism through the nuclear envelope has been demonstrated in nuclear export of large ribonucleoprotein complexes during Drosophila neuromuscular junction formation, indicating a widespread presence of a novel concept of cellular nucleo-cytoplasmic transport.