Researchers discover mechanism behind Ebola's immune system evasion

Researchers recently revealed how the Ebola virus, a pathogen considered to be a Category A bioterrorism agent by the U.S., disarms the adaptive immune system.

Scientists with the University of Texas Medical Branch at Galveston found that Ebola short-circuits the immune system by employing proteins that work together to shut down cellular signals related to interferon. The researchers found that by disrupting the activity, the virus is able to prevent the full development of dendritic cells that could trigger an immune response to the virus.

"Dendritic cells typically undergo a process called 'maturation' when they're infected by a virus - they change shape and present antigens on their surface that tell T-cells to attack that particular virus, thus generating an adaptive immune response," Alexander Bukreyev, the senior author of the paper, said. "But Ebola prevents dendritic-cell maturation and produces a severe infection without an effective adaptive immune response. We found that its ability to do this depends on several specific regions of two different proteins."

Bukreyev's research team discovered the mechanism after experimenting with a series of procedures related to a clone of the Ebola Zaire virus. The team introduced mutations into the genetic code of the virus at four locations thought to generate immune response-related proteins. They found the altered viruses were unable to suppress human dendritic cell maturation.

"We saw two very interesting things," Bukreyev said. "First, that these mutations restore maturation of dendritic cells very effectively, and second, that a mutation in even one of these genetic domains makes the virus unable to suppress maturation. That means that the virus needs multiple combined effects in order to undermine the immune system in this way."

The scientists conducted the study at UTMB's biosafety level 4 facility. The results of the study were published in the Journal of Virology.

The U.S. Centers for Disease Control considers all filoviruses, including Marburg and Ebola, to be Category A bioterrorism agents. Ebola has up to a 90 percent mortality rate in humans.