A team of researchers have discovered the interaction between an Ebola virus protein and a protein in human cells that may be an important key to unlocking the pathway of replication of the killer disease in human host in a study recently published in the journal Cell.
Earlier research used a protein interaction map to narrow down host and virus protein interactions and then using a yeast system and an artificial proxy virus system proved the theory of this particular protein-protein interaction. However, scientists needed to use replicating virus and human immune cells to test the clinical significance of the finding.
"The interaction is important if you can show functional significance of what it does to the virus in cells that have clinical relevance," the author stressed. "If you can figure out the mechanism within these cells, then you can potentially manipulate it and stop the disease progression."
Authors used affinity tag-purification mass spectrometry (AP-MS) to generate an EBOV-host protein-protein interaction (PPI) map. They 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.
The results demonstrate the therapeutic potential of biologics that target this interface and identify additional PPIs that may be leveraged for novel therapeutic strategies.
Inhibiting Ebola Virus Replication!
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