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Induced IL-10 Splice Altering Approach to Antiviral Drug Discovery

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https://ir.library.oregonstate.edu/concern/articles/rv042v839

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  • Ebola virus causes an acute hemorrhagic fever lethal in primates and rodents. The contribution of host immune factors to pathogenesis has yet to be determined and may reveal efficacious targets for potential treatment. In this study, we show that the interleukin (IL)-10 signaling pathway modulates Ebola pathogenesis. IL-10 [superscript - / -] mice and wild-type mice receiving antisense targeting IL-10 signaling via disrupting expression through aberrant splice altering were resistant to ebola virus infection. IL-10 [superscript - / -] mice exhibited reduced viral titers, pathology, and levels of IL-2, IL-6, keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-1 α and increased interferon (IFN)-γ relative to infected wild-type mice. Furthermore, antibody depletion studies in IL-10 [superscript - / -] mice suggest a requirement for natural killer cells and IFN-γ for protection. Together, these data demonstrate that resistance to ebola infection is regulated by IL-10 and can be targeted in a prophylactic manner to protect against lethal hemorrhagic virus challenge.
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  • Panchal, R. G., Mourich, D. V., Bradfute, S., Hauck, L. L., Warfield, K. L., Iversen, P. L., & Bavari, S. (2014). Induced il-10 splice altering approach to antiviral drug discovery. Nucleic Acid Therapeutics, 24(3), 179-185. doi:10.1089/nat.2013.0457
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  • 24
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  • 3
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  • Support from Postgraduate Research Participation Program at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRID) administered by the Oak Ridge Institute for Science and Education and the U.S. Department of Energy and the U.S. Army Medical Research and Materiel Command (USAMRMC). This work was supported by multiple contracts to Sarepta Therapeutics, Inc. by the Joint Project Manager-Transformational Medical Technologies Initiative (HDTRA1-07-C-0010).
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