LIGHT, A NEW MEMBER OF THE TNF SUPERFAMILY, AND LYMPHOTOXIN-ALPHA ARELIGANDS FOR HERPESVIRUS ENTRY MEDIATOR

Herpes simplex virus (HSV) 1 and 2 infect activated T lymphocytes by a ttachment of the HSV envelope glycoprotein D (gD) to the cellular herp esvirus 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 n ew member of the TNF superfamily. LIGHT is a 29 kDa type II transmembr ane protein produced by activated T cells that also engages the recept or 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.