Another piece of the puzzle of the Ebola virus

A team of researchers has discovered the interaction between an Ebola virus protein and a human cell protein that could be an important key to unlocking the replication pathway of the deadly disease in the human host. Scientists at the Texas Biomedical Research Institute have collaborated nationally with scientists from the Gladstone Institutes, UC San Francisco and Georgia State University for a recently published study in the journal Cell.

Scientists around the world are trying to identify potential targets for Ebola, a haemorrhagic fever that has already killed 347 people in the last outbreak in the Democratic Republic of Congo. Thousands of people have died of the Ebola virus since the outbreak of an epidemic in West Africa four years ago.

Olena Shtanko, Ph.D., researcher at Texas Biomed, describes this new work as a "turning point for understanding how Ebola replication is modulated." His role in the project was to validate and verify if the interaction between an Ebola protein called VP 30 and a host protein (human) called RBBP6 is involved in the life cycle of the virus. Dr. Shtanko worked on this project in the laboratory of Dr. Robert Davey, a former Texas Biomed scientist, currently at Boston University.

California researchers had previously used a protein interaction map to refine protein-virus interactions, and then use a yeast system and an artificial proxy virus system to prove the theory of this particular protein-protein interaction. However, scientists had to use human viruses and immune cells that were being replicated to test the clinical significance of the discovery.

"The interaction is important if you can show the functional meaning of what it does for the virus in cells that have clinical relevance," Shtanko said. "If you can understand the mechanism in these cells, you can potentially manipulate it and stop the progression of the disease."

Eusondia Arnett, Ph.D., researcher at Texas Biomed, and Dr. Larry Schlesinger, President and CEO of Texas Biomed, both TB researchers, have expertise in the use of macrophage (immune) cells. ) taken from donated blood samples. "We have been able to capitalize on our macrophage experience to overexpress and under-express RBBP6 (host) protein to create an effective model for this important Ebola research," said Arnett.

By overexpressing and under-expressing RBBP6, Shtanko was able to test the impact of the protein on the growth of Ebola virus in macrophages. Shtanko said the results were striking. When the host protein was under-expressed, viral replication increased exponentially. She has achieved similar results by working with vascular cells, which are also essential for replication of the Ebola virus in an infected patient.

The study was also an example of the team's new scientific environment; This allows researchers to capitalize not only on the resources available at Texas Biomed, but also on the expertise of its cross-functional teams (biology of Ebola and macrophages) to achieve beneficial results.

In the United States, Texas Biomed has one of the few biosafety level 4 labs where scientists can work safely with deadly pathogens, such as the Ebola virus, that cause diseases for which it is not safe. There is no cure. This made it possible to complete the study on human cells using a live virus. And, Shtanko explained, the study's time to study being very short, the availability of Arnett's and Schlesinger's expertise was essential to the creation of the human macrophage cells needed to perform the study. study.

This article has been republished from documents provided by the Texas Biomedical Research Institute. Note: Content may have changed for length and content. For more information, please contact the cited source.

Reference
Protein Interaction Mapping identifies RBBP6 as a negative regulator of Ebola replication. Jyoti Batra et al. Cell, VOLUME 175, NUMBER 7, P1917-1930.E13, DECEMBER 13, 2018, DOI: https://doi.org/10.1016/j.cell.2018.08.044.