FIG. 7.

Model of minimum required receptors for HSV entry. A cartoon model to simplify use of multiple receptors into two minimum types of required receptor interactions to mediate HSV entry. The working model proposes that at least two types of viral glycoprotein and cellular receptor interactions are required to trigger pH-independent virus-cell membrane fusion. Ligands I and II on the virion are in an entry-incompetent state until ligand I (gD) encounters any one of its cell receptors (HVEM, nectin 1, nectin 2, or 3-OS-HS). It then undergoes conformational changes to an entry-active form. These changes would induce rearrangements in viral ligand II to an entry-competent form that can interact with host cell receptor II (B5 and possibly others). Interactions between ligand II and receptor II drive changes in the attachment-fusion complex to eventually trigger localized fusion of the viral envelope and host membrane. Similar to SNARE interactions or interactions in class I viral fusion proteins that contain α-helices, the putative coiled coils in B5 (a type of receptor II) and partner coils in its viral ligand(s) could mediate the interactions required to trigger membrane fusion at entry.