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Single protein, key to ebola virus infection, could aid in drug design
Date:8/24/2011

Research published by two teams of Army scientists and collaborators has identified a cellular protein that plays a critical role in Ebola virus infection. The findings, published online today in separate studies in the journal Nature, suggest a possible strategy for combating one of the world's most deadly viruses.

Ebola causes hemorrhagic fever with case fatality rates as high as 90 percent in humans. The virus is of concern both as a global public health threat and as a potential agent of biological terrorism. Currently there are no available vaccines or therapies to combat the disease. In addition, much is still unknown about the exact mechanism by which Ebola virus invades cells and causes infection.

In one Nature study, scientists from USAMRIID, Albert Einstein College of Medicine, the Whitehead Institute for Biomedical Research, and Harvard Medical School searched for proteins that Ebola virus might use to enter cells. One such cellular protein, known as Niemann-Pick C1 (NPC1), stood out: The team found that if cells don't make NPC1, they cannot be infected by Ebola virus.

According to the authors, the NPC1 protein is embedded within cell membranes, where it helps transport cholesterol within the cell. However, the absence of NPC1 due to gene mutations causes a rare degenerative disorder called Niemann-Pick disease, in which cells become clogged with cholesterol and eventually die.

To confirm the group's finding that NPC1 is crucial for Ebola virus infection, John M. Dye, Ph.D. and colleagues at USAMRIID used mice that were partially deficient in NPC1 expression, challenging the animals with lethal doses of Ebola virus. Remarkably, most of the mice survived the challenge. Other studies using cells from people with Niemann-Pick disease found that those cells also were resistant to Ebola virus infection. In addition, the researchers showed that treating cells with a compound that blocks NPC1 function inhibited i
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Contact: Lori Calvillo
lori.calvillo@amedd.army.mil
US Army Medical Research Institute of Infectious Diseases
Source:Eurekalert

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