HERPES-SIMPLEX VIRUS-1 ENTRY INTO CELLS MEDIATED BY A NOVEL MEMBER OFTHE TNF NGF RECEPTOR FAMILY/

We identified and cloned a cellular mediator of herpes simplex virus ( HSV) entry. Hamster and swine cells resistant to viral entry became su sceptible upon expression of a human cDNA encoding this protein, desig nated HVEM (for herpesvirus entry mediator). HVEM was shown to mediate the entry of several wild-type HSV strains of both serotypes. Anti-HV EM antibodies and a soluble hybrid protein containing the HVEM ectodom ain inhibited HVEM-dependent infection but not virus binding to cells. Mutations in the HSV envelope glycoprotein go significantly reduced H VEM-mediated entry. The contribution of HVEM to HSV entry into human c ells was demonstrable in activated T cells. HVEM, the first identified mediator of HSV entry, is a new member of the TNF/NGF receptor family .