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 hemorrhagic fever in humans and nonhuman primates. The disease pattern includes damage 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 infection. The suggested immunosuppressive properties of EV were examined in this study. We have demonstrated that the whole heat-inactivated virions can dose-dependently suppress human lymphocyte mitogen-stimulated proliferation in vitro. In further analyses, we identified the viral protein responsible for the suppressive effect, and we showed that it was provided by a protein 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 immunosuppressive properties of different portions of GP-125, deletion mutants of GP were designed based on predicted localisation of antigen sites. They were expressed as recombinant proteins and studied in proliferation assays. We identified a 40-amino acid sequence at the N-terminus of GP-125 that exerted a suppressive effect on blastogenesis.
Chepurnov
A A
AA
Laboratory of Extremely Dangerous Viral Infections, State Research Center of Virology and Biotechnology Vector, Koltsovo, Novosibirsk, Region, Russia. chepurnov@vector.nsk.su
Tuzova
M N
MN
Ternovoy
V A
VA
Chernukhin
I V
IV
D029043:Ebolavirus / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009154:Mutation; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D014759:Viral Envelope Proteins