Closing a cell's 'escape hatch' may stop the virus' spread

MONDAY, Dec. 4 (HealthScout) -- Hot on the heels of an announcement of a monkey vaccine, other research into Ebola has yielded a key protein that could lead to new treatments.

It all has to do with plugging a hole in host cells so that newly made copies of the virus can't escape, says a new study.

The Ebola virus invades cells and turns them into factories that copy the deadly organism. Then, a protein sub-unit on the surface of the cells allows the newly minted virus copies to escape and spread the infection. Ideally, shutting off this escape hatch could slow the replication of Ebola and perhaps even contain the disease's characteristic outbreaks.

Ebola's mysterious origins lie somewhere in the jungles of Africa and Asia. In Africa, the disease has surfaced in several villages since the disease was first identified in 1976. Most recently, Ebola has appeared in Uganda, and by the end of November, the World Health Organization had tallied 354 cases and 140 deaths in that outbreak.

Experts believe that initial infections occur through contact with an infected animal. Ebola is transmitted by direct contact with the blood, secretions, organs or semen of an infected organism.

Once infected, patients develop fever, weakness, muscle pain, headache and sore throat. Vomiting, diarrhea, rash, kidney and liver dysfunction, and both internal and external bleeding follow this. Death generally occurs within two to 21 days, and currently, doctors can do little for patients with this highly infective virus, other than replacing lost fluids. Ninety percent of victims die, and the course of the disease is so rapid that it kills faster than it can spread in a sort of lethal variety of self-containment.

Microbiologists at the University of Pennsylvania and the University of Texas are behind this latest discovery, which appears in the most recent issue of the Proceedings of the National Academy of Sciences.

"Any time people are losing their lives, it's urgent," says lead author Ronald Harty, an assistant professor of pathobiology in Philadelphia. "I know [Ebola] isn't worldwide or that widespread, but the potential that it could be is always there. Basically, Ebola is just a plane ride away from almost anywhere in the world."

Like all viruses, Ebola must replicate inside of a living cell, and then the new copies have to escape -- in a process called "budding" -- from the infected cell so that they can spread.

"What we found is that the VP40 protein is believed to play a key role in the release of Ebola virus from the infected cell," says Harty. In fact, the study isolated a specific region of the VP40 protein made of four chemical building blocks called amino acids, which the researchers believe is crucial to the virus budding process.

Harty and his team found that when they worked with cells in cultures and chemically encouraged the VP40 protein without any viruses involved, the VP40 protein would bud on its own, "almost like a virus-like particle," says Harty.

Furthermore, the researchers showed that if they created mutations in the protein, they could significantly reduce the ability of the protein to bud -- suggesting that this approach could be used with Ebola.

"This may represent a potential target for the development an anti-viral agent…to basically slow down or inhibit the release of Ebola virus from the cells," says Harty. "If one could do this -- slow down the replication of the virus -- it may give the body's immune system enough time to develop an immune response and perhaps clear the virus."

A major question remaining to be answered, says Ebola researcher Nancy Sullivan, is whether such a therapy would be safe. "If you inhibit the function of the viral proteins, sometimes you're also inhibiting the function of essential cellular proteins," says Sullivan, a research fellow at the National Institutes of Health in Bethesda, Md. "That's the drawback of most anti-virals."

Harty admits that he doesn't know whether targeting the VP40 sub-unit would create side effects. "We would hope that's not the case. It's a very small [protein], and the idea may be to develop a very small molecule inhibitor, and obviously not to cause any bad side effects." Harty says that future studies will address this issue.

(From HealthScout)