HERPESVIRUS SAIMIRI OPEN READING FRAME-14, A PROTEIN ENCODED BY A T-LYMPHOTROPIC HERPESVIRUS, BINDS TO MHC CLASS-II MOLECULES AND STIMULATES T-CELL PROLIFERATION

Herpesvirus saimiri (HVS) is an oncogenic, lymphotropic, gamma-herpesv irus that transforms human and simian T cells in vitro and causes lymp homas and leukemias in various species of New World primates. Nucleoti de sequence analysis of the HVS genome revealed an open reading frame with 22% amino acid identity to the mouse mammary tumor virus 7 supera ntigen, In this study, we demonstrate that this open reading frame, HV S14, encodes a heavily glycosylated protein that is secreted, Both the HVS14 present in the supernatant of transfected cells and a chimeric HVS14.Fc fusion protein were found to bind to heterodimeric MHC class II HLA-DR molecules, The supernatant from HVS14-transfected cells indu ced the proliferation of human PBMC, which could be specifically inhib ited by HVS14-specific mAbs. Purified peripheral blood T cells were in duced to proliferate in the presence of accessory cells and HVS14-cont aining supernatant, Whereas the HVS14 protein stimulated T cell prolif eration, the HVS14.Fc fusion protein blocked proliferative responses t o soluble Ags in vitro. Collectively, these data indicate that HVS14 c an function as an immunomodulator that may contribute to the immunopat hology of HVS infection.