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Penn scientists find a protein that inhibits Ebola from reaching out to infect neighboring cells
Date:3/4/2008

PHILADELPHIA - Scientists at the University of Pennsylvania School of Veterinary Medicine have identified a protein, ISG15, that inhibits the Ebola virus from budding, the process by which viruses escape from cells and spread to infect neighboring cells. This study shows for the first time how ISG15 slows the spread of Ebola virus budding, an observation that could help explain how ISG15 successfully inhibits other viruses, including HIV-1 and herpes simplex virus type I. The findings, reported in the current issue of the Proceedings of the National Academy of Sciences, offer the promise of future treatments for Ebola outbreaks that now prove fatal for as many as 90 percent of victims.

According to the Penn Vet research team, ISG15 inhibits budding in an indirect way, by blocking the behavior of a particular host cell protein which is used by Ebola and other viruses to efficiently escape from cells. ISG15 specifically inhibits the host protein, Nedd4, used by the viral protein VP40 to escape from cells and allow for virus spread.

Inhibit the proteins used by a virus to reproduce and you are inhibiting the virus itself, Ronald Harty, lead author of the study and associate professor in the Department of Pathobiology at Penn Vet, said. Without host Nedd4, the Ebola virus still buds and attacks, but it doesnt bud as well. The long-term goal of our research is to understand the interplay between host and virus, with the hope of creating an anti-viral drug or inhibitor, much like how Tamiflu doesnt cure the flu but slows down the viral process, Harty said. The drug would be designed to dampen or slow down viral budding to allow an infected persons immune system to fight back.

The Ebola virus VP40 protein is the key player in the process of virus assembly and release from infected cells. VP40 buds from mammalian cells independent of other viral proteins, and efficient release of VP40 virus-like particles, VLPs, requires interactions with hos
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Contact: Jordan Reese
jreese@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

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