Ebolavirus' Soft Spot Uncovered

The discovery of a lone protein that resides on the surface of the Ebolavirus could pave the way for new treatments that could render impotent a virus that, though rare, can kill up to 90% of the people it infects.

Researchers at the Scripps Research Institute (La Jolla, CA, USA) discovered that the so-called Ebolavirus glycoprotein (known as the ‘spike protein'), first discovered a decade ago, is wrapped in benign carbohydrates that mask the virus' deadliness, allowing it to elude immune system scouts. The researchers made their discovery of the crystal structure of the glycoprotein by studying the bone marrow of a survivor of a 1995 Ebola outbreak in Kikwit (Democratic Republic of the Congo), and found that the trimeric Ebolavirus glycoprotein was bound to a neutralizing antibody. They then uncovered a putative receptor-binding site located deep in the chalice-shaped structure of Ebola's glycoprotein that latches onto the surface of host cells and thus gains entry into the cells. Access to the receptor site is restricted by a glycan cap and a protruding mucin-like domain. The discovery could pave the way for drugs designed to see through that protective coating and trigger the immune system to attack the virus before it can enter the cells. The study was published in the July 10, 2008, issue of Nature.

"It's the only thing that the virus puts on its surface that is absolutely critical for attaching to a host and driving into that host for infection,” said co-author Erica Ollmann Saphire, Ph.D., an assistant professor in the department of immunology. "The structure of the glycoprotein shows us the very few sites on its surface that are not cloaked by carbohydrate; these [sites] are the chink in the armor, or the Achilles' heel, that we can target antibodies against.”

Ebola is an incurable disease that was first discovered in 1976 in western Sudan and the eastern part of the Democratic Republic of the Congo (then known as Zaire). A person acquires the virus through contact with the bodily fluids of someone already infected. It can take from two days to three weeks for symptoms of Ebola to appear. The disease presents itself with a fever, muscle aches, and a cough before progressing to severe vomiting, diarrhea, and rashes, along with kidney and liver problems. Death generally occurs as the result of either one or a combination of dehydration, massive bleeding, and kidney and liver failure. The World Health Organization (WHO, Geneva, Switzerland) has so far documented 1,850 cases of Ebola, mostly in sub-Saharan Africa; only 600 (32%) of the victims survived. Since 1994, outbreaks of the virus have increased fourfold.


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