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Frozen Ebola virus reveals its deadly spike

REUTERS

10 a.m. July 9, 2008


Centers for Disease Control and Prevention
Transmission electron micrograph of Ebola virus.
WASHINGTON – Researchers who have managed to freeze the Ebola virus and make images of the spike it uses to infect cells said Wednesday they hope their work may lead to a treatment or vaccine for the deadly microbe.

The researchers have a picture of the so-called spike protein, used by many viruses to get into the cells they infect.

Ebola's spike protein is concealed, which may help explain why the virus is so deadly, said Erica Ollmann Saphire, of the Scripps Research Institute in La Jolla, California, who led the study.

“It cloaks itself with human carbohydrates,” Ollman Saphire said in a telephone interview.

“It's kind of like Harry Potter wrapped in an invisibility cloak. But there are three or four little sites peeking out,” she added.

These may provide a target for a drug or vaccine, or perhaps an immune-based treatment for Ebola, she said.

“We actually have the roadmap to figure out where the chinks in its armor are,” Ollman Saphire said.

Ebola hemorrhagic fever is rare, but there is no good treatment, no cure and no vaccine, and the virus usually kills between 50 percent and 90 percent of its victims.

It is spread when people come into contact with the bodily fluids of a patient. As with other hemorrhagic fevers, patients die from dehydration, bleeding, and shock.

The latest outbreak, which ended in February in Uganda, was unusually mild, killing 37 people out of 149 infected.

A previous outbreak in Uganda in 2000 killed more than half of 425 people infected and a 2006 outbreak in neighboring Congo infected 264 people, killing 187.

YEARS OF WORK

While rare, doctors are keen to find a way to treat Ebola and related viruses such as Marburg.

Ollmann Saphire said it took years to get the virus to crystallize so an image could be taken.

Researchers used an antibody taken from a survivor of a 1995 outbreak in Zaire, which killed 250 out of 315 people infected. Scripps researcher Dennis Burton isolated the antibody, an immune system protein, from the patient's bone marrow.

What they finally saw surprised them.

The spike protein has two sub-units called gp1 and gp2 which wrap around one another oddly, they reported in the journal Nature.

“The site is buried under this tree-like canopy of carbohydrates,” said Ollmann Saphire. This appears to help cloak it from the body's immune cells.

“It is a fascinating little beast,” she said. “It has evolved all these strategies to achieve its various dastardly goals while hiding.”

Viruses are small organisms, usually with only a handful of genes. They must hijack a living cell to replicate themselves.

But viruses are also wrapped up tightly, with only one or two structures that can be affected by the body's immune-fighting cells, or by drugs.

With Ebola, the spike protein may be the only accessible target, Ollmann Saphire said.

“Now we can make a movie of all the different gymnastics that the protein goes through ... in driving the infection,” she said.


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