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Publication

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

Cell | 2018

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.

Pubmed ID: 30550789 RIS Download

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Associated grants

Agency: NIAID NIH HHS, United States
Id: T32 AI060537
Agency: NIAID NIH HHS, United States
Id: R01 AI120694
Agency: NIAID NIH HHS, United States
Id: R21 AI166736
Agency: NIAID NIH HHS, United States
Id: R01 AI114814
Agency: NIGMS NIH HHS, United States
Id: P50 GM082250
Agency: NIAID NIH HHS, United States
Id: U19 AI109945
Agency: NIAID NIH HHS, United States
Id: U19 AI106754
Agency: NIAID NIH HHS, United States
Id: P01 AI063302
Agency: NIAID NIH HHS, United States
Id: R01 AI143292
Agency: NIAID NIH HHS, United States
Id: U19 AI109664
Agency: Howard Hughes Medical Institute, United States
Agency: NIAID NIH HHS, United States
Id: U19 AI135990

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RRID:SCR_001672

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RRID:SCR_008539

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RRID:SCR_014212

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RRID:SCR_014558

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