Here we demonstrate that sGP can function to absorb anti-GP antibodies. Furthermore, the recent finding that EBOV mutates to a predominantly non-sGP-forming phenotype in cell culture, while the mutant virus reverts to an sGP-forming phenotype in vivo, suggests that sGP is critical for EBOV to survive in its infected host.
The function of the Ebola virus (EBOV) secreted glycoprotein (sGP) has been long debated, and the fact that sGP production is conserved among all known EBOV species strongly indicates an important role in the viral life cycle. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP 1,2 response resulting in strong cross-reactivity with sGP. We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP 1,2, thereby allowing it to absorb anti-GP 1,2 antibodies. In this study, we immunized mice with DNA constructs expressing GP 1,2 and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP 12 antibodies, but only from mice that have been immunized by sGP. However such a role has not been conclusively determined for the Ebola virus sGP. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. In addition to its surface glycoprotein (GP 1,2), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space.
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