Tim-1 is an attractive target for combating Ebola


The recent Ebola virus epidemic in West Africa is the most serious outbreak of Ebola virus disease in history. More than 27,000 cases and 11,000 deaths have been reported to date. A number of therapeutic agents and candidate vaccines are being developed, but currently, supportive care is still the primary treatment for Ebola virus disease. Understanding how the virus causes illness would help to develop effective therapies to treat or prevent the disease.

Now, a team of scientists from the University of Texas Medical Branch, the University of Washington, and National Institutes of Health have demonstrated that Ebola virus directly binds to the Tim-1 protein on T cells, inducing a cytokine storm that causes tissue damage. Described in mBio on 26 September 2017, the findings provide clues to the pathogenesis of Ebola virus disease and suggest Tim-1 as an attractive therapeutic target for treating the lethal disease.

How does Ebola kill people? Numerous effects have been made to unravel the mystery. It is now clear that it is not the virus that kills but the uncontrolled immune reaction. At the end stage of Ebola virus disease, numerous pro-inflammatory cytokines are secreted, a condition known as cytokine storm. A cytokine storm is a potentially fatal immune response to highly pathogenic invaders.

Previous studies have shown that activation of T cells is associated with cytokine storm in Ebola virus disease. In addition, the Tim-1 protein has been identified as a receptor for Ebola virus, and an antibody directed against the receptor protein is able to block infection by Ebola virus.

In the current study, the team demonstrated that Ebola virus binds to Tim-1 on T cells, activating T cells and causing the cytokine storm. Tim-1-deficient mice were protected from Ebola infection: they showed reduced disease severity and higher survival rates. The results indicate that Tim-1 is involved in the pathogenesis of Ebola virus disease. Therefore, targeting Tim-1 may inhibit cytokine storm, providing a way to combat Ebola.
 
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