IOWA STATE—The Zaire Ebola virus has an uncanny ability to disguise itself, making it unrecognizable—and deadly—as an invading virus.
When most viruses invade a cell, they start to make RNA in order to replicate. When the healthy host cell senses the replicating RNA, it starts to activate anti-viral defenses that halt replication and eventually help clear the viral infections.
A research team led by Gaya Amarasinghe, assistant professor of biochemistry, biophysics, and molecular biology at Iowa State University, had previously solved the structure of a critical part of an Ebola protein known as VP35, which is involved in host immune suppression.
The team has now discovered that Ebola encoded VP35 protein actually masks the replicating viral ribonucleic acid (RNA), so the cell doesn’t recognize that there is an invading virus.
“The question with Ebola has always been ‘Why can’t host cells mount an immune response against the Ebola virus, like they do against other viruses?'” he says.
“The answer is, ‘If the cell doesn’t know that there’s an infection, it cannot build up any response.’ So our work really gets at the mechanism Ebola infection and immune evasion.”
One of the reasons Ebola, in particular the strain isolated from Zaire, is so deadly is that the host cells don’t have any immune response when the virus enters the cell, explains Amarasinghe.
Working with virologist Christopher Basler at the Mt. Sinai School of Medicine in New York City, Amarasinghe investigated how the structural findings match up with how the proteins function inside the cell.
“Our initial structure that we solved in 2008 was key to expanding our knowledge, but the structure was just part of the equation, and when we put it together with the functional studies, everything made sense,” Amarasinghe says.
The research appears in the current issue of the journal Nature Structural and Molecular Biology and is available as an advanced online publication.
For the study, Amarasinghe focused on a specific part of the Zaire Ebola VP35 protein that he thought looked unusual.
As testing results came in, he found that the suspect region of the protein was binding with, or neutralizing, the part of the host cell that triggers the immune system in the cell.
“The interesting thing about the Ebola virus is that it doesn’t let cells even get started to defend themselves,” he explains.
“This hides the (viral) RNA from being recognized by the host cell. This is a powerful immune evasion mechanism.”
Researchers from Mount Sinai School of Medicine; the Albert Einstein College of Medicine, New York City; the University of Texas Southwestern Medical Center, Dallas; and the Berkeley National Laboratory, Calif., contributed to the study, which was funded by the Roy J. Carver Charitable Trust, National Institutes of Health, and the Midwest Regional Center for Excellence for Biodefense and Emerging Infectious Disease Research.
Iowa State University news: www.news.iastate.edu/