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Bleeding symptom leads scientists to intracellular trafficker's role in virus propagation
Date:11/14/2013

t to bind and enter host cells. After defining the human proteins that interact with each viral GP, the researchers examined which host proteins were common to both viruses, selecting one for further investigation ERGIC-53, one of only three known intracellular cargo receptors.

"People who don't make ERGIC-53 have combined Factor V and Factor VIII deficiency, a mild form of hemophilia," Botten says. "Despite having this condition, these individuals are in good health, provided they get synthetic clotting factors or fresh frozen plasma following a major trauma or surgery. So in essence, people don't need ERGIC-53 to survive, which makes this an attractive antiviral target."

That initial connection the fact that people with this deficiency bleed and people who get these types of hemmorhagic fever viruses bleed was what got the researchers interested in ERGIC-53; they believed this protein could be important for both the propagation of these viruses as well as their ability to make people bleed.

The team got to work, seeking to determine just how ERGIC-53 might impact virus propagation. They quickly discovered that ERGIC-53 is absolutely essential for the propagation of arenaviruses. Additionally, "we found a new means for ERGIC-53 to associate with its viral partners binding to arenavirus GPs via a previously unknown, lectin-independent mechanism," Botten says. In fact, the team discovered that ERGIC-53 also interacts with the GPs of additional pathogenic RNA viruses such as orthomyxoviruses (e.g., influenza), coronaviruses (e.g., SARS), and filoviruses (e.g., Ebola and Marburg). Importantly, they discovered that virus particles decorated with Ebola or SARS virus GPs also critically depend on ERGIC-53 to be infectious.

New information centering on viral particles, which are produced when a person gets infected, were another important finding of the study. The group determined that ERGIC-53 is a "virion component" it gets into t
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Contact: Jennifer Nachbur
jennifer.nachbur@uvm.edu
802-656-7875
University of Vermont
Source:Eurekalert

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