Wall Street Journal - March 4, 2002
Marilyn Chase, Staff Reporter

Ebola kills roughly 80% of those who contract it, usually causing them to bleed to death in a few weeks. Since its discovery in 1976, the virus has killed 1,000 people, according to the World Health Organization. Recent Ebola outbreaks in the Republic of Congo and neighboring Gabon in central Africa have killed several dozen people. The virus's mysterious appearances, rapid course and lack of treatment have made it a daunting challenge for public health -- and a potential weapon for terrorists.

Now, a research team says it has answered important basic questions about how Ebola, and a related virus, Marburg, commandeer human cells. Their findings shed light on possible ways to design drug therapies. The Ebola virus, shaped like a shepherd's crook, targets tiny fat platforms called "lipid rafts" that float atop the membrane of human cells. These cholesterol-rich rafts are the viruses' gateway into cells, the assembly platform for making new virus particles, and the exit point where new virus particles bud.

This virus-like particle, the harmless hollow shell of the Ebola virus, may one day be useful in creating an Ebola vaccine. The particle has been disarmed of its genetic material and is unable to replicate.

The team's report, set to be published Monday in the Journal of Experimental Medicine, "is highly significant," says Eric Freed, principal investigator in the laboratory of molecular microbiology at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health in Bethesda, Md. "It adds another human pathogen to the growing list of viruses that use lipid rafts."

The findings add new insight into the life cycle of viruses and how they subvert human cellular mechanisms. It is a critical early step toward one day creating drugs that would stop viruses from replicating. Ebola and Marburg, both members of a family of hemorrhagic-fever viruses called filoviruses, share the reproduction strategy of viruses ranging from measles and influenza to HIV, which causes AIDS. Their ability to traffic aboard lipid rafts may help them evade the human immune system, researchers speculate.

One of the researchers, Sina Bavari, at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Md., says, "By understanding how Ebola and Marburg are entering into and budding from the cells, it gives us an avenue to come up with new therapeutics that would alter these pathways." Dr. Bavari's co-author is M. Javad Aman, of Clinical Research Management Inc. in Frederick, Md.

The push to probe Ebola has assumed greater urgency since the Sept. 11 terror attacks, as fears have grown about the existence of weaponized forms of Ebola or Marburg. Such bioterror weapons were in development within the former Soviet Union, according to Kenneth Alibek, a Soviet bioweapons scientist who defected to the U.S. and wrote the 1999 book "Biohazard."

Says Dr. Bavari, "It doesn't take a Nobel laureate to figure out that something so deadly could be transformed into a bioterror agent." Yet-to-be-developed vaccines and antiviral drugs could be critical elements of bioterror defense against the viruses.

Because their targets, the lipid rafts, are made of fat, known agents such as the popular cholesterol-lowering statin drugs may offer one possible model for new drug therapies. Antifungal drugs, such as nystatin and filipin, that break up fat could be other possible models.

In their research, Drs. Bavari and Aman produced harmless copies of the Ebola virus that, it turns out, may be a possible vaccine candidate. The virus-like particles, known as VLPs, are hollow protein shells, gutted of their virulent genome. The researchers say the hollow proteins could elicit an immune defense, because they signal the body that an Ebola invasion is under way without actually causing disease.

"You're basically fooling the body," Dr. Bavari says, "but the virus cannot replicate itself." The hollow-protein model is one approach being used in the search for a vaccine for HIV. Future studies will examine whether such a strategy is safe and effective against Ebola and Marburg, he adds.

The researchers say their creation of the hollow VLPs could allow Ebola research to take place more freely in laboratories across the country, on regular lab benches outfitted with suction hoods, to prevent the escape of particles. At present, scientists have to wear space suits and work behind air-locked doors in high-containment Biosafety Level 4 labs when handling live Ebola virus.

Another National Institutes of Health researcher working on Ebola, Gary J. Nabel, of the Vaccine Research Center at NIAID, applauds the report. Dr. Nabel has published studies showing that Ebola vaccine created using experimental "naked DNA" -- the opposite of the hollow VLPs, in a way -- protected monkeys against lethal Ebola infection when given with a booster shot of the vaccine. His team is partnering with Vical Inc., a San Diego biotech company, to produce the vaccine prior to launching studies of its safety in humans.

"People are waiting with bated breath for a drug or vaccine," Dr. Nabel said. "These [studies] show that we're on the road that will get us there."

Write to Marilyn Chase at marilyn.chase@wsj.com
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