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Penn Vet research identifies compounds that control hemorrhagic viruses
Date:5/1/2014

uence known as PTAP, which is present in proteins that play important roles in the budding of Ebola and HIV, and the human protein Tsg101. This interplay is important for the virus to break free of the host cell's plasma membrane and continue infecting other cells. If this interaction is blocked, many of the viruses will remain tethered to the cell membrane, unable to perpetuate the infection.

Though the viruses under study are too dangerous to manipulate in the Penn Vet lab, Harty's team was nonetheless able to examine the interactions between host and viral proteins by looking at what are known as virus-like particles, or VLPs, produced using the virus' matrix protein, of which PTAP is a part.

"If you take just the matrix protein, it can self-assemble and bud from cells on its own as a VLP," Harty said. "Because that particle is composed only of the matrix protein and no genetic material, it's not infectious. It's a neat assay that we can use in our lab to learn more about the budding process."

Using this assay, Harty's team screened a library of various small molecules to find some that would block the interaction between PTAP and Tsg101. They found a promising candidate called compound 0013.

Testing the effectiveness of this molecule in their VLP assay, they found that it reduced the ability of the virus to bud off from human cells in culture by more than 90 percent and was similarly effective against proteins found in Ebola and HIV.

As a final confirmation of the compound's potential to stop a virus from spreading, they tested it against an actual virus: the nonpathogenic vaccine strain of the Junin virus. The pathogenic strain of Junin virus causes Argentine hemorrhagic fever and is considered a potential bioterrorism agent. The researchers found that it significantly decreased viral budding in a dose-dependent manner.

The second paper used an analogous strategy to try to block another viral-host interacti
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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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