Deadly Ebola Virus' Secret Weapon Discovered, Infection Short-Circuits Immune System

Researchers believe that they may have located the mechanism behind the cause of the deadly Ebola virus.

Although the exact origin or location of the virus is unknown, evidence and nature of similar viruses is believed to be animal-borne, with four to five subtypes occurring in an animal host native to Africa, according to the Centers for Disease Control. This severe and often-fatal disease in humans and many primates, including monkeys, gorillas and chimpanzees, was first recognized in 1976.

The virus is one of two members of a family of RNA viruses called the Filoviridae. There are five identified subtypes of Ebola virus. Four of the five have caused disease in humans: Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast and Ebola-Bundibugyo. The fifth, Ebola-Reston, has caused disease in nonhuman primates, but not in humans.

Scientists from the University of Texas Medical Branch at Galveston have determined that Ebola short-circuits the immune system using proteins that work together to shut down cellular signaling related to interferon. Disruption of this activity, the researchers found, allows Ebola to prevent the full development of dendritic cells that would otherwise 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," said UTMB professor Alexander Bukreyev, according to a press release. "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 group made the discovery after a series of procedures that started with a clone of the Ebola Zaire virus strain. Working under maximum-containment conditions in a biosafety level 4 facility in UTMB's Galveston National Laboratory, the team introduced mutations into the virus' genetic code at four locations thought to generate proteins that affected immune response.

They then infected human dendritic cells with each of the resulting new strains and compared the results with those produced by unmutated Ebola Zaire. Each of the four new viruses, they found, was unable to suppress 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 findings for the discovery are found this month now online in the Journal of Virology.