How Ebola virus disables the body's immune defenses

Ebola virus disease is one of the most devastating infectious diseases known to exist, with previous outbreaks resulting in high fatality rates. The particularly aggressive nature of Ebola virus stems from its ability to rapidly disarm the infected person’s immune system by blocking the development of a virus-specific adaptive immune response.

White blood cells are an important part of our immune system. Lymphopenia happens when the white blood T cell count in the bloodstream is lower than normal — in fact, the extent of lymphopenia is one of the strongest indicators of how severe the Ebola infection will become.

“People who survive an Ebola infection are able to maintain their T cell levels over the course of the infection whereas low T cell levels are nearly universally seen in fatalities,” said senior author Alex Bukreyev, a UTMB virologist in the departments of pathology and microbiology and immunology. “The trouble is that we’ve never understood how this T cell depletion occurs, so we set out to answer this question.”

Using cellular biology and genetic approaches, the researchers demonstrated for the first time how the Ebola virus can attach to, enter and infect T cells and what happens afterward. Although the virus is confined within the infected T cells, they become stressed to the point where the body destroys them. This contributes to the lymphopenia that’s linked to disease severity.

“With this new information, we’re planning to investigate the role of these processes in Ebola-induced white blood cell death, immunosuppression and disease development in general,” said Bukreyev.

Other authors include UTMB’s Patrick Younan, Rodrigo Santos, Palaniappan Ramanathan, Mathieu Iampietro, Michelle Meyer and Vsevolod Popov as well as Andrew Nishida and Mukta Dutta from the University of Washington, Tatiana Ammosova and Sergei Nekhai from Howard University as well as Michael Katze from the National Primate Research Center.

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