Figure 11. Schematic representation of proposed herpes virus envelopment pathways.

(1) Capsids bud at the INM into the PNS acquiring tegument and an envelope covered with a dense coat. These perinuclear virions are transported into the RER and further via Golgi transitions (1a) or the ERGIC (“hug-and-kiss”, 1b) into Golgi cisternae where they are packaged into transport vacuoles, which are detached from Golgi membranes by fission. The dense coat is shed off while vacuoles are transported to the cell periphery for exocytotic release of uncoated virions into the extracellular space. (2) Capsids gain direct access to the cytoplasmic matrix via dilated nuclear pores (dNP), and are transported to any site of the Golgi complex. They either bud into Golgi cisternae and vacuoles, respectively (2a) or are enveloped by a process designated wrapping (2b) that involves budding and concomitant formation of a small transport vacuole engulfing a single virion. Capsids can also be enveloped by endosomal membranes (2c). Occasionally, capsids may bud at the OM or RER (2d), and the resulting virions are intraluminally transported as in pathway 1. Finally, vacuoles derived by fission from Golgi membranes or from membranes of vacuoles or endosomes transport virions to the cell periphery and release them into the extracellular space via exocytosis. The dense coat, which derived during the budding process at the INM and ONM and probably protects the viral envelope from fusion with membranes the virions are transported along, is shed of (de-coating) in transport vacuoles at latest when virions are released into the extracellular space. During budding at Golgi cisternae and vacuoles, a dense rim of tegument is closely attached to the inner layer of the viral envelope. However, no dense coat is formed so that spikes (glycoproteins) are readily seen in high resolution micrographs.