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Ebola protein blocks early step in body's counterattack on virus
Date:8/13/2014

niversity School of Medicine in St. Louis. "By determining the structure of an eVP24 in complex with a cellular transporter, we learned how Ebola does this."

Ebola Defeats Immune Defenses Early in Infection

The study spotlights the part of the body's defense system that fights infection called innate immunity, the mix of proteins and cells that most quickly recognizes an invasion by a virus. This part of immunity keeps a virus from quickly reproducing inside cells.

To trigger an effective, early response to viral infection, interferons must pass on their signal to other cells. This occurs through other messengers inside cells as part of interferon signaling pathways, with the last of these messengers turning on genes inside the nuclei of cells to drive the immune response.

The current study determined the structure of eVP24 when bound to its cellular targets, transport proteins called karyopherins. The study used these structures to show how, in place of interferon's natural downstream signal carrier phosphorylated STAT1, eVP24 docks into the karyopherins meant to escort STAT1 into cell nuclei where it turns on interferon-targeted genes. By elegantly interfering at this stage, eVP24 cripples innate immunity to cause EVD.

In 2006, Dr. Basler and colleagues found that the Ebola virus suppresses the human immune response through eVP24, but not how. Through of combination of molecular biology techniques, cell studies and tests that reveal protein structures, the current team led by Dr. Amarasighe defined the molecular basis for how eVP24 achieves this suppression.

Understanding exactly how the Ebola virus targets the interferon pathway could help guide drug development moving forward. Dr. Basler describes how it may be possible to find an antibody or molecule that interferes with eVP24, or that works around its competition with STAT1, such that treatment of patients with extra interferon, long used against the
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Contact: Greg Williams
newsmedia@mssm.edu
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine
Source:Eurekalert

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