A team of scientists led by researchers from the University of California, San Francisco, J. David Gladstone Institutes, Georgia State University and Northwestern University Feinberg School of Medicine has discovered a human protein that could one day lead to an effective therapy against Ebola virus. The discovery is reported in the journal Cell.
Ebola virus (green) infects human cells much more easily when you remove a protein called RBBP6. Image credit: Northwestern University.
Ebola virus is an enveloped RNA virus that has caused repeated outbreaks of severe, often deadly human disease over the past four decades.
Like other viruses, it invades host cells and uses them to replicate, usurping cellular processes to build viral proteins, which eventually become new copies of the virus.
“There are some promising experimental vaccines and drugs for Ebola virus — some which are being used on an emergency basis in people — but still nothing is officially approved for use in humans,” said Georgia State University’s Professor Christopher Basler, co-lead author of the study.
“There’s still a need to explore potential new drugs for Ebola and related viruses.”
In the new study, Professor Basler and co-authors used mass spectrometry to search for interactions between human proteins and Ebola virus proteins.
“There’s still much we don’t know about how the virus grows, how it causes severe disease and how components of the host cell interact with the virus,” he said.
“In the study, we were trying to get a more comprehensive understanding of how the viral proteins interact with the host cell proteins to understand why the virus causes disease and to find new ways to block virus growth.”
RBBP6 helps fight Ebola virus by interfering with the virus replication cycle. Image credit: Batra et al, doi: 10.1016/j.cell.2018.08.044.
The team found strong evidence for an interaction between the Ebola virus protein VP30 and the human protein RBBP6.
Further structural and computational analysis narrowed the interaction down to a small, 23-amino acid-long peptide chain.
“This small group of amino acids alone is sufficient to disrupt the Ebola virus life cycle,” said co-author Dr. Judd Hultquist, a researcher at Northwestern University Feinberg School of Medicine.
“If you take that peptide and put it into human cells, you can block Ebola virus infection. Conversely, when you remove the RBBP6 protein from human cells, Ebola virus replicates much faster.”
“Viruses are parasites that rely on the cell they infect to reproduce,” Professor Basler said.
“We have 194 human proteins that we’ve identified interacting with Ebola virus proteins. Some of these will help the virus grow.”
“Many of these interactions haven’t been previously implicated in facilitating the replication of Ebola virus or other viruses. That by itself is interesting. It means we’ve uncovered new ways in which the virus interacts with its host cell.”
“We decided to first focus on one interaction in particular. The Ebola virus protein VP30 was found to interact with RBBP6.”
“What we found was striking. Two parts of the virus, a protein called VP30 and another called nucleoprotein (NP), must interact for the virus to grow. Our cells make a protein, RBBP6, that prevents VP30 from finding NP. Instead, VP30 finds RBBP6. This reduces virus growth.”
“If we can design a drug that would mimic what RBBP6 is doing, then we’d have a new way to suppress Ebola virus growth.”
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Jyoti Batra et al. 2018. Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication. Cell 175 (7): 1917-1930; doi: 10.1016/j.cell.2018.08.044
