Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication

Cell. 2018 Dec 13;175(7):1917-1930.e13. doi: 10.1016/j.cell.2018.08.044.


Ebola virus (EBOV) infection often results in fatal illness in humans, yet little is known about how EBOV usurps host pathways during infection. To address this, we used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. We uncovered 194 high-confidence EBOV-human PPIs, including one between the viral transcription regulator VP30 and the host ubiquitin ligase RBBP6. Domain mapping identified a 23 amino acid region within RBBP6 that binds to VP30. A crystal structure of the VP30-RBBP6 peptide complex revealed that RBBP6 mimics the viral nucleoprotein (NP) binding to the same interface of VP30. Knockdown of endogenous RBBP6 stimulated viral transcription and increased EBOV replication, whereas overexpression of either RBBP6 or the peptide strongly inhibited both. These results demonstrate the therapeutic potential of biologics that target this interface and identify additional PPIs that may be leveraged for novel therapeutic strategies.

Keywords: Ebola virus; RBBP6; RNA viruses; VP30; antiviral factor; host-pathogen interactions; protein-protein interactions; virus-host interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins* / chemistry
  • Carrier Proteins* / genetics
  • Carrier Proteins* / metabolism
  • Crystallography, X-Ray
  • DNA-Binding Proteins* / chemistry
  • DNA-Binding Proteins* / genetics
  • DNA-Binding Proteins* / metabolism
  • Ebolavirus / physiology*
  • HEK293 Cells
  • HeLa Cells
  • Hemorrhagic Fever, Ebola / genetics
  • Hemorrhagic Fever, Ebola / metabolism*
  • Hemorrhagic Fever, Ebola / pathology
  • Humans
  • Protein Interaction Mapping
  • Transcription Factors* / chemistry
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism
  • Ubiquitin-Protein Ligases
  • Viral Proteins* / chemistry
  • Viral Proteins* / genetics
  • Viral Proteins* / metabolism
  • Virus Replication / physiology*


  • Carrier Proteins
  • DNA-Binding Proteins
  • Transcription Factors
  • VP30 protein, ebola virus
  • Viral Proteins
  • RBBP6 protein, human
  • Ubiquitin-Protein Ligases