A Novel Mechanism of Host Immune Evasion by Ebola Virus

Ebola virus Ebola virus is the causative agent of Ebola Hemorrhagic Fever (EHF), a disease with up to 90 percent mortality. While human outbreaks of Ebola hemorrhagic fever have been confined to Africa, Ebola virus infections in bats, the presumed natural reservoir of the virus, have also been detected in Europe and Asia.

The high lethality of the disease, combined with its short incubation period and the lack of vaccines or effective treatments, makes Ebola virus a significant public health threat as well as a potentially devastating biological weapon. Efforts to develop a vaccine against Ebola virus have been met with limited success, and it is likely that the virus employs complex immune evasion mechanisms that present unique challenges for vaccine design. Understanding these evasion mechanisms is a critical first step in developing an effective vaccine.

In this study, the authors examined the role of a protein secreted in large quantities by Ebola virus-infected cells. The protein shares regions with a membrane protein that the virus expresses on its surface and uses to initiate the infection process. The authors studied antibodies generated by immunizing mice with the viral surface protein and/or the secreted protein. They determined that the secreted protein can selectively drive induction of antibody responses to itself and also compete for antibodies to the viral surface protein that would otherwise bind to and inactivate the virus.

The results suggest that immunity induced by a vaccine may need to reach a sufficient threshold to effectively neutralize the incoming virus to protect against Ebola virus infection. These findings raise new challenges for Ebola vaccine design, as vaccines will most likely have to be tailored to overcome or avoid the ability of the secreted decoy protein to interfere with host immune responses. Such approaches could enable the development of more efficacious vaccines to prevent Ebola virus infection.

 

Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus. (2012) PLoS Pathog 8(12): e1003065. doi:10.1371/journal.ppat.1003065
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. 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. Here we demonstrate that sGP can function to absorb anti-GP antibodies. More importantly, instead of simply passively absorbing host antibodies, sGP actively subverts the host immune response to induce cross-reactivity with epitopes it shares with membrane-bound GP1,2. Immune subversion by sGP represents a distinct mechanism from the use of secreted antigens as antibody decoys, an immune evasion tactic previously proposed for other viruses, and should be an important consideration for future EBOV vaccine design efforts since vaccines may need to be specifically tailored to avoid subversion.

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