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Ebola Decoy Protein Fools Immune Response

English: Biosafety level 4 hazmat suit: resear...

Biosafety Level 4 (BSL-4) lab where Ebola research is conducted. (Photo: Wikipedia)

The Ebola virus simultaneously elicits fear and fascination. It causes a horrifying death for its victims, who suffer from a hemorrhagic fever. Even though Ebola is primarily transmitted via direct contact with infected organisms or their fluids, recent research suggests that Ebola may also be transmitted through the air. Creepy enough as all that is, new research demonstrates that Ebola may have yet another trick up its sleeve.

But first, a little background:

The surface of the Ebola virus is covered with glycoprotein (GP), which binds host cells, allowing the virus to enter. Ebola is an RNA-based virus, which means its genetic information is stored in RNA, not DNA. Thus, it has to use a special enzyme (an RNA-dependent RNA polymerase) to create mRNA (the molecule which is translated into protein). This error-prone enzyme is vital to generating GP, which comes in two forms. The first is a full-length version, which is generated by a mysterious process known as RNA editing. Essentially, the polymerase enzyme purposefully mis-transcribes the RNA genome, about 20% of the time, to generate an "edited" mRNA from which the full-length version of GP is translated. The other 80% of the time, editing does not occur, and a shorter GP is produced. This short GP is secreted outside of the virus-infected cell and is known as secretory GP (sGP). 

Now, researchers have demonstrated that sGP is a clever invention. The Ebola virus appears to subvert the host's immune response by using sGP as a decoy to divert away precious antibodies.

Full-length GP is prominently displayed on the surface of the virus, and a successful human antibody response needs to target this protein. But, Ebola doesn't want that to happen, as it would neutralize the virus and prevent it from infecting cells. To counter this immune assault, Ebola deploys sGP, which subverts the immune response in two ways.

The first way is by passively absorbing antibodies directed at the full-length GP. Full-length GP and sGP share many structural features, so antibodies directed against the full-length GP can be tricked into binding the decoy sGP.

But, there's a second, more insidious way that sGP can subvert the immune response. It can trigger the proliferation of B-cells (antibody-producing cells) that preferentially bind sGP. In other words, sGP redirects the immune response to produce antibodies more suitable for binding the decoy sGP, not the full-length GP. Because so much sGP is produced by Ebola, this decoy protein skews the immune response toward attacking it, leaving the full-length GP on its surface free of neutralizing antibodies and, hence, free to attack host cells. The authors refer to this new pathogenic mechanism as "antigenic subversion."

The researchers caution that such viral treachery may have implications for vaccine design.

Source: Mohan GS, Li W, Ye L, Compans RW, Yang C (2012). "Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus." PLoS Pathog 8(12): e1003065. doi:10.1371/journal.ppat.1003065.


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