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When ebola is engulfed by a healthy cell, the virus is contained in a vesicle. But the virus forms a fist and smashes its way into the cell’s cytoplasm, where it can effectively turn the cell into a factory for virus production. (Credit: Global Panorama/Centers for Disease Control and Prevention/Flickr)

Africa

Ebola forms a ‘fist’ and punches its way into cells

Researchers have discovered how the deadly Ebola virus—a disease that many fear may be used for bioterrorism—smashes its way into healthy cells and turns them into virus factories.

Outbreaks of the virus, which kills 90 percent of the people it infects, are now occurring in the African countries of Guinea, Liberia, and Sierra Leone. In addition to the toll on human life in these areas, there is significant concern that it could spread elsewhere around the world.

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Published in the Journal of Virology, the new findings offers important insight into how the virus works its way into cells and also identifies an important target to block the infection process.

After Ebola is engulfed by the cell, it is contained within a vesicle where it can do no harm. But the virus quickly escapes the vesicle, and now scientists say they understand how. The pH level inside the vesicle triggers the surface glycoprotein on the virus to form a “fist” that lets the virus punch its way into the cell’s cytoplasm, where it can effectively turn the cell into a factory for virus production.

Havoc in cells

“If it stayed in the vesicle, it would be not much of a problem. The cell could digest it,” says Lukas Tamm, a researcher in in the molecular physiology and biological physics department at University of Virginia.

“But then it escapes from that internal vesicle into the body of the cell, and that’s when the danger happens. It does that by fusing its own membrane with that cellular vesicle membrane, and that lets the RNA of the virus out into the cell to replicate, to basically cause havoc in those cells.”

Ironically, when the virus approaches a cell, what becomes the fist looks more like an outstretched hand. The virus forms its fist and identifies amino acids within the virus critical for the clenching to occur. “If you lose those,” Tamm says, “it would always be in the extended hand formation.”

Closer to stopping ebola

To test his findings, Tamm collaborated with Judith M. White, a researcher in the cell biology department, who has developed virus-like particles that act like Ebola, but pose no danger in the laboratory. The hypothesis held true—not just in test tubes, but in live cells as well. Peter M. Kasson of the molecular physiology and biological physics department then created a computer model of the process. The result is a remarkable new understanding of Ebola infection.

By understanding the process, researchers say they are significantly closer to being able to stop Ebola—and perhaps other viruses with similar structures as well.

“Once you have visualized the molecular shape changes that these structures undergo upon cell entry, you can see what molecules or potential anti-viral drugs could interfere with this process,” Tamm says.

“You have these contacts that need to be made to make the clenching of the fist happen—if you could find a molecule that throws a wrench into the gears of that mechanism, you could actually block that from happening.”

Source: University of Virginia

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