Suppressive effect of Ebola virus on T cell proliferation in vitro is provided by a 125-kDa GP viral protein

Ebola virus (EV), an extremely infectious pathogen, causes severe hemorrhag ic fever in humans and nonhuman primates. The disease pattern includes dama ge of parenchymal cells of vital organs in association with hemostatic and immune disorders. Vaccination with the inactivated virions does not provide an effective immune protection against the disease. The inadequate immune response may be directly caused by the virus, and, hence, it may presumably be crucial in the pathogenic process and prophylactic treatment of Ebola i nfection. The suggested immunosuppressive properties of EV were examined in this study. We have demonstrated that the whole heat-inactivated virions c an dose-dependently suppress human lymphocyte mitogen-stimulated proliferat ion in vitro. In further analyses, we identified the viral protein responsi ble for the suppressive effect, and we showed that it was provided by a pro tein corresponding to a 125-kDa envelope glycoprotein (GP-125). The protein alone inhibited lymphocyte proliferation, whereas the other viral proteins were without significant effect on blastogenesis. To determine the immunos uppressive properties of different portions of GP-125, deletion mutants of GP were designed based on predicted localisation of antigen sites. They wer e expressed as recombinant proteins and studied in proliferation assays. We identified a 40-amino acid sequence at the N-terminus of GP-125 that exert ed a suppressive effect on blastogenesis. (C) 1999 Elsevier Science B.V. Al l rights reserved.