Herpesvirus entry mediator

Herpesvirus entry mediator (HVEM), also known as TNFRSF14 (tumor necrosis factor receptor superfamily member 14), is a protein that in humans is encoded by the TNFRSF14 gene. It is a member of the tumor necrosis factor receptor superfamily and plays a key role in the entry of herpesvirus into cells.

Structure

The HVEM protein is a type I membrane protein that is expressed in many immune cells, including T cells, B cells, and monocytes. It consists of an extracellular domain containing four cysteine-rich repeats, a transmembrane domain, and a cytoplasmic domain that contains a death domain motif.

Function

HVEM acts as a receptor for herpes simplex virus (HSV) and pseudorabies virus (PRV), facilitating their entry into cells. It interacts with the viral glycoprotein D (gD), which is present on the surface of the virus. This interaction triggers a series of events that lead to the fusion of the viral envelope with the cell membrane, allowing the virus to enter the cell.

In addition to its role in viral entry, HVEM also plays a role in immune regulation. It can interact with several ligands, including LIGHT and BTLA, to modulate immune responses. For example, the interaction between HVEM and BTLA can inhibit T cell activation, providing a mechanism for immune tolerance.

Clinical significance

Mutations in the TNFRSF14 gene can lead to a variety of immune disorders. For example, loss-of-function mutations have been associated with an increased risk of autoimmune diseases, such as rheumatoid arthritis and lupus. On the other hand, gain-of-function mutations can lead to the development of certain types of cancer, including non-Hodgkin lymphoma and cutaneous T cell lymphoma.

Research

Research is ongoing to develop drugs that can block the interaction between HVEM and its ligands, with the aim of preventing herpesvirus infection or modulating immune responses. Several small molecule inhibitors and monoclonal antibodies are currently in preclinical or early clinical development.

File:Herpesvirus entry mediator.png

Structure of the herpesvirus entry mediator protein.

See also

• Herpesvirus
• Tumor necrosis factor receptor
• Herpes simplex virus
• Pseudorabies virus