Herpes simplex virus type 1 glycoprotein D inhibits T-cell proliferation

Herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) binds to its cellular receptor, herpesvirus entry mediator (HVEM), to enter into activated T cells. Since gD is expressed on the cell surface of activated T cells after infection and can interact with HVEM, a co-stimulatory molecule for T cells, we hypothesized that the membrane-bound gD can exert an immunomodulatory effect on activated T cells. In this report, we demonstrated the following: (1) The gD expression was detected on the cell surface of activated T cells after HSV-1 infection. (2) Recombinant soluble gD protein or gD-expressing mouse fibroblasts inhibited T-cell proliferation that was induced by OKT3 [anti-CD3 monoclonal antibody (mAb)]. (3) The co-expression of gD and HVEM resulted in the inhibition of the nuclear factor (NF)-kappaB activation that was induced by the HVEM overexpression. Taken together, our results suggest that the inhibitory effect of gD may be due to its ability to actively inhibit the signaling pathway that is mediated by HVEM on the cell surface level, which may be a novel immune evasion mechanism that is utilized by HSV-1.