| Literature DB >> 30550789 |
Jyoti Batra1, Judd F Hultquist2, Dandan Liu3, Olena Shtanko4, John Von Dollen5, Laura Satkamp5, Gwendolyn M Jang5, Priya Luthra6, Toni M Schwarz7, Gabriel I Small3, Eusondia Arnett8, Manu Anantpadma4, Ann Reyes4, Daisy W Leung3, Robyn Kaake5, Paige Haas5, Carson B Schmidt5, Larry S Schlesinger8, Douglas J LaCount9, Robert A Davey4, Gaya K Amarasinghe3, Christopher F Basler10, Nevan J Krogan11.
Abstract
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.Entities:
Keywords: Ebola virus; RBBP6; RNA viruses; VP30; antiviral factor; host-pathogen interactions; protein-protein interactions; virus-host interactions
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Year: 2018 PMID： 30550789 PMCID： PMC6366944 DOI： 10.1016/j.cell.2018.08.044
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850