Herpesvirus infections are widely spread throughout the world population. Herpes simplex virus (HSV) belongs to the α-herpesvirus subfamily. There are two main types of HSV, HSV-1 and HSV-2, which infect humans. HSV-2 mainly causes genital lesions, whereas HSV-1 is involved in both oral and genital infections. In epithelial cells, the heterodimer gE/gI is required for the cell-to-cell spread of the virus, by sorting nascent virions to cell junctions. Once the virus reaches the cell junctions, virus particles can spread to adjacent cells extremely rapidly through interactions with cellular receptors that accumulate at these junctions. Implicated in basolateral spread in polarized cells. In neuronal cells, gE/gI is essential for the anterograde spread of the infection throughout the host nervous system.