4.6 Article

An immunotoxin targeting Ebola virus glycoprotein inhibits Ebola virus production from infected cells

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PLOS ONE
卷 16, 期 1, 页码 -

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PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0245024

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资金

  1. Battelle Memorial Institute
  2. US National Institute of Allergy and Infectious Diseases (NIAID) [HHSN272200700016I]
  3. Laulima Government Solutions, LLC
  4. NIAID [HHSN272201800013C]
  5. Laulima Government Solutions, LLC [HHSN272201800013C]
  6. Division of Intramural Research of NIAID [ZIA AI000538-30]

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The immunotoxin 6D8-PE38 specifically targets Ebola virus-infected cells and effectively inhibits viral production, showing promise as a potential antiviral intervention for Ebola virus disease.
Ebola virus (EBOV), a member of the mononegaviral family Filoviridae, causes severe disease associated with high lethality in humans. Despite enormous progress in development of EBOV medical countermeasures, no anti-EBOV treatment has been approved. We designed an immunotoxin in which a single-chain variable region fragment of the EBOV glycoprotein-specific monoclonal antibody 6D8 was fused to the effector domains of Pseudomonas aeruginosa exotoxin A (PE38). This immunotoxin, 6D8-PE38, bound specifically to cells expressing EBOV glycoproteins. Importantly, 6D8-PE38 targeted EBOV-infected cells, as evidenced by inhibition of infectious EBOV production from infected cells, including primary human macrophages. The data presented here provide a proof of concept for immunotoxin-based targeted killing of infected cells as a potential antiviral intervention for Ebola virus disease.

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