Ebolaviruses

REFERENCE: Dias et al. “A shared structural solution for neutralizing ebolaviruses.” (2011) Nature Structural and Molecular Biology 18(12) pgs 1424 – 1427.

                Five types of ebolaviruses have been identified: Sudan, Ebola, Reston, Bundibugyo, and Tai Forest.  The Sudan and Ebola forms cause the predominant amount of human deaths and recently a new variant of the Sudan virus has been found in the Gulu district of Uganda.  While many monoclonal antibodies exist, only a handful can neutralize Ebola virus and none can neutralize Sudan virus.  In a recent Nature Structural and Molecular Biology publication, Dias et al. discuss their development of a neutralizing antibody for Sudan virus and a subsequent crystal structure of it bound to the Gulu-Sudan variant protein GP_1,2.

                GP_1,2 (glycoprotein) is a viral trimeric receptor solely responsible for bringing ebolavirus into a host cell.  The protein is so named because the entire amino acid sequence is expressed then cleaved to create GP₁ and GP₂.  However, these two proteins remain attached to each other via a disulfide bond until the viral membrane fuses with the endosomal membrane.   

                The monoclonal antibody developed here, referred to as 16F6, recognized native Sudan virus GP_1,2 and their work indicated that binding of 16F6 alone was enough to block infection.  The epitope for the antibody was revealed by X-ray crystallography to be at the base of the trimer (Figure 11.1).  Further work showed that Sudan virus could still attach to host cells and be internalized, which left the authors to speculate that the antibody is either inhibiting another unidentified factor or it is blocking an additional necessary conformational change in GP_1,2 that leads to successful infection.  

                The final sentence of their paper summarizes a possible far-reaching conclusion from their work as “...for viruses in general, successful immunotherapy and vaccine design may depend on targeting antibodies that anchor glycoprotein subunits together and prevent the conformational changes required for fusion.”