A research team led by Gaya Amarasinghe, an assistant professor of biochemistry, biophysics and molecular biology, had previously solved the structure of a critical part of an Ebola protein known as VP35, which is involved in host immune suppression.
Amarasinghe and his research team now know how VP35 is able to do it.
When most viruses invade a cell, they start to make RNA in order to replicate.
When the healthy host cell senses the replicating RNA, the host cell starts to activate anti-viral defenses that halt replication and eventually help clear the viral infections.
What Amarasinghe and his group have discovered is that Ebola virus encoded VP35 protein actually masks the replicating viral ribonucleic acid (RNA), so the cell doesn't recognize that there is an invading virus.
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, said Amarasinghe.
"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 said. ]
"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."
The collaborative approach taken by Amarasinghe enabled him to team up with virologist Christopher Basler at the Mt. Sinai School of Medicine, New York City, to investigate how the structural findings match up with how these 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 said.
The current research describing the protein-RNA complex structure, which was solved by using non-infectious VP35 protein, and associated functional studies is published in the current issue of the journal Nature Structural and Molecular Biology and is available as an advanced online publication.
These findings build on Amarasinghe's research published in the journal Proceedings of the National Academy of Sciences of the United States of America last January.
In his current research, 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 said. "This hides the (viral) RNA from being recognized by the host cell. This is a powerful immune evasion mechanism."
Amarasinghe, along with Daisy Leung, associate scientist; Mina Farahbakhsh, undergraduate student; Eshwar Ramanan, graduate student; Luke Helgeson, undergraduate student; and Richard Honzatko, professor; all from Iowa State's biochemistry, biophysics and molecular biology department, together with Kathleen Prins, graduate student, and Basler, associate professor; from Mount Sinai School of Medicine; JoAnn Tufariello; assistant clinical professor of the Albert Einstein College of Medicine, New York City; Dominika Borek, instructor; and Zbyszek Otwinowski from the University of Texas Southwestern Medical Center, Dallas; and Jay Nix from the Berkeley National Laboratory, Calif., co-authored this study.
Work in the Amarasinghe laboratory was funded in part 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. X-ray crystallographic data were collected at the Advanced Light Source beamline 4.2.2., and the Advanced Photon Source Structural Biology Center Sector 19 beamlines.
Gaya Amarasinghe | EurekAlert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy