University of Texas researchers announced on Thursday that they have discovered a key biochemical link in the process by which the Ebola Zaire virus infects cells -- a critical step to finding a way to treat the deadly disease produced by the virus.
Ebola produces severe and often fatal hemorrhagic fever in its victims and inflicts mortality rates close to 90 percent in some outbreaks. No vaccine or antiviral therapy has been developed against the virus.
The research team tied Ebola's cellular invasion mechanism to aseries of biochemical reactions called the phophoinositide-3 kinase pathway (named for an enzyme found in the cell membrane). By activating the PI3 kinase pathway, they found, an Ebola virus particle tricks the cell into drawing it into a bubble-like compartment known as an endosome, which is pulled, together with the virus, into the cell. Then -- at a critical point -- the virus bursts free from the endosome and begins to reproduce itself.
However, if the PI3 kinase pathway is shut down -- as the researchers did with a drug designed for that purpose -- Ebola virus particles can't escape from the endosome, and the disease process comes to a halt.
"The nice part about identifying entry mechanisms is you can prevent the virus from infecting the cell," said Robert Davey, the lead researcher. "You can stop the whole show before it even gets started."
Davey noted that while other viruses had been found that activated the PI3 kinase pathway, Ebola was the first with envelope proteins that had been seen doing so. In addition, he said, it was the first virus to be discovered interacting with thePI3 kinase pathway in order to enter cells, which could have profound implications.
In addition, a new generation of drugs are being developed that target PI3 kinase, since the enzyme is often activated in cancers. It is possible that these could also be used to defend against Ebola virus.
(Xinhua News Agency September 5, 2008)