Fig 1.
HSV-1 envelope proteins and their roles in entry and membrane fusion.
(A) HSV-1 entry into cells requires the coordinated efforts of the receptor-binding glycoprotein gD (RCSB PDB: 2C36), the heterodimer gH/gL (RCSB PDB: 3M1C), and the fusogen gB (RCSB PDB: 5V2S). For gB, only the structure of its postfusion conformation is known, so the prefusion conformation of HSV-1 gB is depicted schematically. Interactions of these essential proteins with cellular coreceptors can influence the entry of HSV-1 into a cell. (B) HSV-1 contains 15 proteins within its lipid envelope, 12 glycosylated (gB, gC, gD, gE [RCSB PDB: 2GIY], gG, gH, gI, gJ, gK, gL, gM, gN) and three unglycosylated (UL20, UL45, US9). The roles of the 11 “nonessential” envelope proteins, with respect to entry route selection, are minimally understood. Glycoproteins gC and gG promote entry at the apical side of polarized epithelial cells. The glycoprotein gK promotes entry into neurons by fusion at the plasma membrane. Other envelope proteins (gE, gI, gM, gN, and UL45) have roles in cell-to-cell spread and membrane fusion but have not yet been assigned any roles in entry. 3-OS-HS, 3-O-sulfated-heparan sulfate; HSV-1, herpes simplex virus type 1; HVEM, herpes virus entry mediator; PDB, Protein Data Bank; PILRα, paired immunoglobulin-like type 2 receptor alpha; RCSB, Research Collaboratory for Structural Bioinformatics.