Induced IL-10 Splice Altering Approach to Antiviral Drug Discovery Public Deposited

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

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by Mary Ann Liebert, Inc. and can be found at:  http://www.liebertpub.com/nat.

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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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  • description.provenance : Submitted by Erin Clark (erin.clark@oregonstate.edu) on 2015-03-02T17:34:41Z No. of bitstreams: 1 MourichDanMicrobiologyInducedIL-10Splice.pdf: 643162 bytes, checksum: d5ca94c77b6605508bb8107fc89a1855 (MD5)
  • description.provenance : Approved for entry into archive by Erin Clark(erin.clark@oregonstate.edu) on 2015-03-02T17:34:56Z (GMT) No. of bitstreams: 1 MourichDanMicrobiologyInducedIL-10Splice.pdf: 643162 bytes, checksum: d5ca94c77b6605508bb8107fc89a1855 (MD5)
  • description.provenance : Made available in DSpace on 2015-03-02T17:34:56Z (GMT). No. of bitstreams: 1 MourichDanMicrobiologyInducedIL-10Splice.pdf: 643162 bytes, checksum: d5ca94c77b6605508bb8107fc89a1855 (MD5) Previous issue date: 2014-05-16

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