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In a breakthrough that could eventually help tame one of the deadliest viruses known to man, researchers have laid bare the key to Ebola's power: a lone protein that resides on its surface. The discovery paves the way for new treatments that target and destroy the designated culprit, rendering impotent a virus that, though rare, can kill up to 90 percent of the people it infects.
The so-called Ebola virus glycoprotein, or "spike protein," was first discovered a decade ago and has been a target for scientists attempting to design vaccines and therapies to prevent it from infecting cells. But, until now, researchers did not understand the protein's structure—and thus, the best way to attack it.
"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," says Erica Ollmann Saphire, an immunologist at The Scripps Research Institute in La Jolla, Calif., and a co-author of the study appearing today in Nature.
Researchers discovered that the compound is wrapped in benign carbohydrates that mask the virus's deadliness, allowing it to elude immune system scouts. (The human immunodeficiency virus, HIV, that causes AIDS also has this trait.) The good news: the discovery could pave the way for drugs designed to see through that protective coating—and trigger the immune system to attack.
"The structure of the glycoprotein shows us the very few sites on its surface that are not cloaked by carbohydrate," Ollmann Saphire explains. "These [sites] are the chink in the armor, or the Achilles' heel, that we can target antibodies against."
"We now have a much better handle on how in the world this virus gets into cells," Ollmann Saphire says. "We also have new maps we can use to develop strategies to fight against it."
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). It seems to have arisen in the rain forests of Africa and parts of the western Pacific. 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 due to leaky blood vessels, kidney and liver failure. The World Health Organization has documented 1,850 cases of Ebola (mostly in sub-Saharan Africa) since its discovery; only 600 (32 percent) of the victims survived.
Researchers made their latest finding by studying the bone marrow of a lucky survivor of a 1995 Ebola outbreak in Kikwit, a city in the southwestern part of the Democratic Republic of the Congo. They found the glycoprotein attached to an antibody (a protein unleashed by the immune system to fight viruses) in the marrow, the soft core of bones where red blood cells are manufactured.
According to Ollmann Saphire, there is a receptor located deep in the bowl-shaped structure of Ebola's glycoprotein that latches onto the surface of host cells and tricks a protein there into granting the virus entry. Once inside the cells, the fast-acting Ebola co-opts their machinery to make millions of copies of itself and floods the person's bloodstream.
Judith White, a microbiologist at the University of Virginia, says that arming researchers with the protein structure that Ollmann Saphire's group has described will allow them to "nip [the virus] in the bud," by beating down Ebola before it enters its host. (Most antivirals target viruses such as HIV after they're already inside a host cell.)
"For those of us in the trenches trying to study the virus entry, and the immune reactions to the virus, and how to prevent virus entry, and how to come up with better immune therapies," she says, "this gives us all new eyes to [solving] those problems."
