During an epidemic in 2014, the Ebola virus claimed more than 11,000 lives in West Africa. Now, a new outbreak of the deadly disease threatens residents in eastern Democratic Republic of the Congo. While there isn’t yet a cure for Ebola, scientists at Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute recently made two discoveries that could help us understand how the virus infects the body.
In the first study, Staff Scientist Olena Shtanko, PhD studied a cellular pathway called “autophagy,” which means “self-eating.” This pathway normally occurs inside the cell and destroys invading foreign material or recycles necessary nutrients. But Dr. Shtanko’s team, working with a live Ebola virus, discovered, to their surprise, that autophagy was also active near the surface of the cell.
The Ebola virus exploits autophagy to induce another process to gain entry to the cell. That process is macropinocytosis, a poorly understood mechanism during which the cell surface remodels to form membrane extensions around virions (virus particles), eventually closing to bring them into the interior of the cell. It is as if the cell reaches out and grabs the virus, bringing it inside its membrane, where virus proteins can begin to replicate.
“We were stunned to find that Ebola virus is using autophagy regulators right at the surface of the cell,” Shtanko stated. “Knowing that these mechanisms work together, we can start finding ways to regulate them.”
Shtanko believes that drugs targeting the interplay between the two processes could potentially be developed to treat Ebola and other health conditions not associated with viruses. The regulation of the autophagy proteins could be used to fight complex diseases where macropinocytosis is disrupted, such as cancer and Alzheimer’s.
Shtanko’s commitment to fighting Ebola has spanned multiple studies. Another team she worked with discovered the interaction between an Ebola virus protein and a protein in human cells. This interaction may be a key part of replication of the killer disease in human hosts.
During the study, researchers tested whether the interaction between an Ebola virus protein called VP 30 and a host (human) protein called RBBP6 influenced the life cycle of the virus. By removing RBBP6 or flooding the cell with it, the scientists found striking results.
When RBBP6n was removed, viral replication went up exponentially compared to when the protein was present. Shtanko said this interaction is significant because if scientists can figure out the process behind this replication, they can potentially manipulate it and stop the disease progression.
Both of these discoveries represent large leaps forward in understanding the Ebola virus and treating and preventing this deadly disease.
