How Ebola Virus Blocks the Immune System

The Ebola virus, in the midst of its biggest outbreak on record, is a master at evading the body’s immune system. But researchers at the Washington University School of Medicine in St. Louis and elsewhere have learned one way the virus dodges the body’s antiviral defenses, providing important insight that could lead to new therapies. The virus has infected approximately 1,800 people since March 2014 in four West African nations and killed more than half of them, according to the World Health Organization. The researchers developed a detailed map of how an Ebola protein, VP24, binds to a host protein that takes signaling molecules in and out of the cell nucleus. Their map revealed that the viral protein takes away the host protein’s ability to carry an important immune signal into the nucleus. This signal helps activate the immune system’s antiviral defenses, and blocking it is believed to contribute significantly to the virus’s deadliness. “We’ve known for a long time that infection with Ebola obstructs an important arm in our immune system that is activated by molecules called interferons,” said senior author Gaya Amarasinghe, Ph.D., assistant professor of pathology and immunology at the Washington University School of Medicine. “Now that our map of the combined structure of these two proteins has revealed one critical way Ebola does this, the information it provides will guide the development of new treatments.” The results appeared online on August 13, 2014 in Cell Host & Microbe. A National Institutes of Health (NIH) grant of up to $15 million, awarded March 1, 2014, is helping Dr. Amarasinghe and other researchers look for drugs to block VP24 and another Ebola protein, VP35.
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