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Scientists uncover Ebola cell-invasion strategy
Date:9/3/2008

GALVESTON, Texas University of Texas Medical Branch at Galveston researchers 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, and it is considered a high-risk agent for bioterrorism. In addition, recent devastating outbreaks hit in Uganda in 2008 and the Democratic Republic of the Congo in 2007.

The UTMB group tied Ebola's cellular invasion mechanism to a series 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 UTMB team 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 UTMB microbiology and immunology associate professor Robert Davey, senior author of a paper on the investigation appearing online in the current issue of the journal PloS Pathogens. "You can stop the whole show before it even gets started."

The researchers did some of their work using the Ebola Zaire virus itself, working in UTMB's Robert E. Shope, MD, Biosafety Level 4 laboratory to ensure their safety. They also conducted experiments using harmless, hollow, virus-like pa
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Contact: Jim Kelly
jpkelly@utmb.edu
409-772-8791
University of Texas Medical Branch at Galveston
Source:Eurekalert

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