Researchers Discover Human Protein That Inhibits Ebola Virus Replication

Researchers Discover Human Protein That Inhibits Ebola Virus Replication

Ebola is a highly contagious enveloped RNA virus that is spread through bodily fluids. Infection with the virus causes Ebola hemorrhagic fever (EHF).

Treatment is primarily concerned with managing the symptoms, which can be severe and often prove fatal. Ebola kills between 25% and 90% of people who are infected, with an average fatality rate of 50%. There have been almost annual outbreaks of the disease in Africa in the past 18 years according to the CDC.

Ebola invades cells and uses the cells’ machinery to replicate and create viral proteins, which become new copies of the virus. Due to the highly infectious nature of the disease and the high fatality rate, treatments for Ebola and diseases caused by similar viruses are desperately needed. While there are some promising vaccines for Ebola currently under development, there is no cure for Ebola and no approved vaccines.

Very little is actually known about the virus, such as how the virus grows, why it causes such severe symptoms, nor how various components of the virus interact with host cells.

A team of researchers from the University of California, San Francisco, Georgia State university, Northwestern University Feinberg School of Medicine, and J. David Gladstone Institutes have been studying the virus to find answers to these questions.

In the latest study, the researchers used mass spectroscopy to identify interactions between Ebola virus proteins and human proteins. The researchers generated a BOV-host protein-protein interaction (PPI) map and uncovered 194 high-confidence EBOV-human PPIs. One human protein (RBBP6) was found to interact with Ebola virus protein VP30 and inhibit the replication of virus.

Specifically, the inhibitory effect was determined to be due to a 23-amino acid peptide chain, which by itself, was capable of disrupting the life cycle of the virus.

“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,” explained Dr. Judd Hultquist, Northwestern University Feinberg School of Medicine researcher and co-author of the study. “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.”

A cure for Ebola may still be a long way off but if a drug can be developed that is capable of mimicking RBBP6 it could be used to suppress Ebola growth, thus reducing the severity of symptoms and could potentially reduce fatalities.

The research is detailed in the paper -Protein Interaction Mapping Identifies RBBP6 as a Negative Regulator of Ebola Virus Replication – which was recently published in the journal Cell. DOI: 10.1016/j.cell.2018.08.044

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