Figure 3.

HSV-1 egress and relevant non-essential proteins. Essential proteins are not depicted. (A) U_L31 and U_L34 form the Nuclear Egress Complex (NEC), which drives the vesiculation of the inner nuclear membrane (INM) and primary envelopment of HSV-1 capsids. (B) Nuclear de-envelopment is mediated by U_L51. Tegument and envelope proteins assemble in a complex network on membranes derived from the trans-Golgi network. (C) HSV-1 capsids undergo cytoplasmic envelopment in a process regulated by multiple non-essential proteins, which involves functional redundancy. After cytoplasmic envelopment, enveloped virions are sorted to the extracellular space, which requires gK. HSV-1 release from the cell membrane can be inhibited by tetherin, which is counteracted by gM. (D) Depending on cell type (e.g., polarized epithelial cells), enveloped virions can disseminate through cell-to-cell spread, in a process that requires U_L7/U_L51 for sorting of virions towards parts of the membrane that contain gE/gI. Virions may spread to adjacent cells by binding to gE/gI receptors in adjacent cells. However, such receptors are unknown.