Research sheds new light on Ebola pathogenesis

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Researchers from the University of Texas Medical Branch at Galveston (TX, USA), University of Washington (WA, USA) and the National Institute of Allergy and Infectious Diseases (MD, USA) have gained new insights into how the immune system is used by Ebola virus to cause infection.

It has previously been demonstrated that Ebola virus affects the host immune system, exacerbating the inflammatory response and causing a ‘cytokine storm’ central to its disease severity; T cells have been implicated in this pathway. In this study, published recently in mBio, the team identified the role of T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) in the development of Ebola.

The researchers utilized genetically engineered mouse models, observing that mice deficient in Tim-1 exhibited increased survival rates and reduced disease severity when infected with Ebola virus, despite a limited decrease in viremia – this suggests the Tim-1 protein is required for pathogenesis. In addition, the team demonstrated that Tim-1 deficient mice had a modified inflammatory response, including changes in serum cytokines and T cell activation.

Author Alexander Bukreyev, form the University of Texas, explained: “Mice that were genetically engineered without Tim-1 became less ill when infected with Ebola virus and only one died, whereas all of the unmodified mice succumbed.”

The researchers then carried out in vitro assays, demonstrating that Ebola virus binds to isolated T cells in Tim-1 dependent manner and providing evidence for its role of  in the induction of the ‘cytokine storm’.

Study author, Patrick Younan (University of Texas), concluded: “Understanding how the invading Ebola virus impacts the host’s immune system is a very important step in developing targeted therapies for Ebola virus disease. The findings of this study indicate that drugs that block Tim-1 could be a potential new treatment for people with Ebola.”

“If we can find a way to limit the inflammatory response known as the ‘cytokine storm’ during Ebola infection, we can potentially improve disease outcome.”

Sources: Younan P, Iampietro M, Nishida A et al. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm. mBio. 8(5) e00845–17 (2017); https://www.utmb.edu/newsroom/article11671.aspx

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