LIGHT, a new member of the TNF superfamily, and lymphotoxin α are ligands for herpesvirus entry mediator

Herpes simplex virus (HSV) 1 and 2 infect activated T lymphocytes by attachment of the HSV envelope glycoprotein D (gD) to the cellular herpesvirus entry mediator (HVEM), an orphan member of the tumor necrosis factor receptor superfamily. Here, we demonstrate that HVEM binds two cellular ligands, secreted lymphotoxin alpha (LT alpha) and LIGHT, a new member of the TNF superfamily. LIGHT is a 29 kDa type II transmembrane protein produced by activated T cells that also engages the receptor for the LT alpha beta heterotrimer but does not form complexes with either LT alpha or LT beta. HSV1 go inhibits the interaction of HVEM with LIGHT, and LIGHT and go interfere with HVEM-dependent cell entry by HSV1. This characterizes herpesvirus go as a membrane-bound viokine and establishes LIGHT-HVEM as integral components of the lymphotoxin cytokine-receptor system.