Herpes simplex virus 1 host cell entry receptors (HSV-1 entry receptors)

Host cell entry receptors for HSV-1 are a diverse group of cell surface molecules that facilitate the multi-step process of viral attachment and penetration into various human tissues. The entry process typically begins with the virus binding to heparan sulfate proteoglycans (HSPG) for initial attachment, followed by the specific interaction of viral glycoprotein D (gD) with one of three primary receptors: Nectin-1 (a cell adhesion molecule), Herpesvirus Entry Mediator (HVEM, a TNF receptor superfamily member), or 3-O-sulfated heparan sulfate. Additionally, other host factors such as PILR-alpha, NMHC-IIA, and MAG interact with viral glycoprotein B (gB) to trigger the fusion of the viral envelope with the host cell membrane. These receptors determine the tissue tropism of the virus, with Nectin-1 being the primary receptor in epithelial and neuronal cells, while HVEM is prominent in lymphoid cells. Because these receptors are essential for the establishment of both lytic and latent infections, they are significant targets for antiviral drug development. Therapeutic strategies include the use of entry inhibitors like docosanol, which disrupts membrane fusion, and experimental agents such as peptides or small molecules that block specific glycoprotein-receptor interactions. However, targeting these host proteins poses challenges due to their endogenous roles in immune signaling and cell-cell adhesion.

Other names

Herpesvirus entry mediator (HVEM)Nectin-13-O-sulfated heparan sulfate (3-OS HS)HveAHveCPoliovirus receptor-related protein 1 (PVRL1)Tumor necrosis factor receptor superfamily member 14 (TNFRSF14)Paired immunoglobulin-like type 2 receptor alpha (PILR-alpha)Non-muscle myosin heavy chain IIA (NMHC-IIA)Myelin-associated glycoprotein (MAG)

Inhibition of viral-host membrane fusion, competitive inhibition of viral attachment to heparan sulfate, and downregulation of receptor expression.