2. Academic Validation
  3. Identification of interferon-stimulated genes that attenuate Ebola virus infection

Identification of interferon-stimulated genes that attenuate Ebola virus infection

  • Nat Commun. 2020 Jun 11;11(1):2953. doi: 10.1038/s41467-020-16768-7.
Makoto Kuroda 1,  Peter J Halfmann 2,  Lindsay Hill-Batorski 1,  Makoto Ozawa 3 4,  Tiago J S Lopes 1,  Gabriele Neumann 1,  John W Schoggins 5,  Charles M Rice 6,  Yoshihiro Kawaoka 7 8 9
Affiliations

Affiliations

  • 1 Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA.
  • 2 Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA. [email protected].
  • 3 Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, 890-0065, Japan.
  • 4 Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, 890-0065, Japan.
  • 5 Department of Microbiology, UT Southwestern Medical Center, Dallas, TX, 75390, USA.
  • 6 Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY, 10065, USA.
  • 7 Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, 53711, USA. [email protected].
  • 8 Division of Virology, Department of Microbiology and Immunology, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, 113-8654, Japan. [email protected].
  • 9 ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, 332-0012, Japan. [email protected].
PMID: 32528005 DOI: 10.1038/s41467-020-16768-7
Abstract

The West Africa Ebola outbreak was the largest outbreak ever recorded, with over 28,000 reported infections; this devastating epidemic emphasized the need to understand the mechanisms to counteract virus Infection. Here, we screen a library of nearly 400 interferon-stimulated genes (ISGs) against a biologically contained Ebola virus and identify several ISGs not previously known to affect Ebola virus Infection. Overexpression of the top ten ISGs attenuates virus titers by up to 1000-fold. Mechanistic studies demonstrate that three ISGs interfere with virus entry, six affect viral transcription/replication, and two inhibit virion formation and budding. A comprehensive study of one ISG (CCDC92) that shows anti-Ebola activity in our screen reveals that CCDC92 can inhibit viral transcription and the formation of complete virions via an interaction with the viral protein NP. Our findings provide insights into Ebola virus Infection that could be exploited for the development of therapeutics against this virus.

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