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Research deciphers Ebola’s methods

By Carolyn Y. Johnson
Globe Staff / August 25, 2011

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Two teams of local scientists revealed new insights yesterday into how Ebola, the deadly virus that riveted readers in “The Hot Zone,’’ infects cells - and how to potentially stop the virus altogether.

Using different techniques, one group led by scientists from the Whitehead Institute for Biomedical Research in Cambridge and another led by Brigham and Women’s Hospital researchers found that a protein that ordinarily is involved in the transport of cholesterol is essential for infection to occur. Researchers took cells from patients with a rare, genetic disease called Niemann-Pick type C1, who have a defective form of that protein and found that the virus could not infect those cells in a laboratory dish.

The findings, published in back-to-back papers in the journal Nature, describe more fully how the deadly virus gains access to cells and points the way to possible strategies to intervene. Both teams also identified compounds that could inhibit Ebola infection, at least in laboratory tests. But the researchers who did the work and an outside scientist cautioned that a therapy was a long way off.

“It’s neat. Scientifically, it’s very exciting,’’ said Thomas Geisbert, a professor of microbiology and immunology at the University of Texas Medical Branch at Galveston. “ “It’s a long way from taking something like this and saying this is a strategy that you would end up using for a drug.’’

What the new research adds is a complete picture of how Ebola - a virulent pathogen that causes hemorrhagic fever - gains access to cells. The virus is known to approach the outside of a cell, which then engulfs the virus by forming a balloon-like enclosure, called an endosome. But for the virus to get into the engine of the cell, it needs to break out of the bubble and enter the cell. Earlier work showed an enzyme produced by the cell, called cathepsin B, cleaved off the cap of a mushroom-shaped Ebola protein. The new work suggests the leftover stalk of that protein needs the host’s Niemann-Pick protein for the virus to enter the cell.

“We think that by knowing these host factors, you’d also have an idea of cellular targets that you could inhibit in order to prevent the virus from entering,’’ said Thijn Brummelkamp, senior author of one of the papers and now a group leader at the Netherlands Cancer Institute.

The Brigham and Women’s researchers screened thousands of compounds to identify a new one that inhibited Ebola virus infection, which led them to understand the Niemann-Pick protein was necessary for infection.

In order to do the work, Boston and Cambridge researchers had to use altered forms of the virus. Work on the real virus was conducted at the US Army Medical Research Institute of Infectious Diseases in Frederick, Md.

“I think this study may have some important consequences for how one thinks about therapy against Ebola infection,’’ said Sean Whelan, a Harvard Medical School associate professor of microbiology and immunobiology who worked with Brummelkamp. “Here’s a target we should go after now therapeutically - and we know this is something we should be able to exploit.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

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