Directed egress of alphaherpesviruses by sorting in the TGN. Alphaherpesvirus glycoproteins accumulate in the TGN, and this process involves the cytoplasmic domains of gE/gI (blue) as well as other viral membrane proteins, such as gM. There is assembly of tegument components around these sites of glycoprotein accumulation and binding of nucleocapsids (red). In epithelial cells, assembly of viral particles occurs selectively in sorting compartments of the TGN that will ultimately be delivered to cell basolateral or lateral surfaces (B), e.g., through gE/gI coupling to μ1B-substituted AP1 clathrin adapters (46). Other viral or cellular membrane proteins are sorted in different domains of the TGN to apical surfaces (A). Virions reach the lateral surfaces of cells in transport vesicles, which fuse with the plasma membrane and deliver virus particles into the space between cells. There are specific interactions of HSV glycoproteins with components of cell junctions—gD with nectins and apparently gE/gI with other molecules—which facilitate entry into adjacent cells. When both cells are infected, there can be accumulation of HSV particles between cells as receptors are blocked. ER, endoplasmic reticulum.