University of Texas Medical Branch at Galveston researchers have discovered a key biochemical link in the process by which the Ebola Zaire virus infects cells — a critical step to finding a way to treat the deadly disease produced by the virus.
Ebola produces severe and often fatal hemorrhagic fever in its victims and inflicts mortality rates close to 90 percent in some outbreaks. No vaccine or antiviral therapy has been developed against the virus, and it is considered a high-risk agent for bioterrorism. In addition, recent devastating outbreaks hit in Uganda in 2008 and the Democratic Republic of the Congo in 2007.
The UTMB group tied Ebola's cellular invasion mechanism to a series of biochemical reactions called the phophoinositide-3 kinase pathway (named for an enzyme found in the cell membrane). By activating the PI3 kinase pathway, they found, an Ebola virus particle tricks the cell into drawing it into a bubble-like compartment known as an endosome, which is pulled, together with the virus, into the cell. Then – at a critical point — the virus bursts free from the endosome and begins to reproduce itself.
However, if the PI3 kinase pathway is shut down — as the UTMB team did with a drug designed for that purpose — Ebola virus particles can't escape from the endosome, and the disease process comes to a halt.
"The nice part about identifying entry mechanisms is you can prevent the virus from infecting the cell," said UTMB microbiology and immunology associate professor Robert Davey, senior author of a paper on the investigation appearing online in the current issue of the journal PloS Pathogens. "You can stop the whole show before it even gets started."
The researchers did some of their work using the Ebola Zaire virus itself, working in UTMB's Robert E. Shope, MD, Biosafety Level 4 laboratory to ensure their safety. They also conducted experiments using harmless, hollow, virus-like particles coated with the critical envelope proteins that activate the PI3 kinase pathway.
Using a unique test created at UTMB that adds a light-emitting molecular beacon, called luciferase, to Ebola viruses and the virus-like particles, the investigators were able to determine exactly when and where each broke out of its bubble, and track its progress.
"Up to that point, it's really a bus ride for these viruses, and PI3 kinase is the bus driver," Davey said. "Whether you're talking about Ebola or Ebola virus-like particles, they've all got the virus envelope proteins that trigger the PI3 kinase pathway, which is the first step of getting the virus onto that bus."
Davey noted that while other viruses had been found that activated the PI3 kinase pathway, Ebola was the first with envelope proteins that had been seen doing so. In addition, he said, it was the first virus to be discovered interacting with the PI3 kinase pathway in order to enter cells, which could have profound implications.
"It's actually triggering the reorganizing of the cell for its own devious outcomes — infecting the cell," Davey said. "But there are other possible outcomes of fiddling around with the PI3 kinase. You can get the cell to move, you can get it to live longer, all advantages for a virus. So I'm sure that this is going to be important in other viruses."
In addition, a new generation of drugs are being developed that target PI3 kinase, since the enzyme is often activated in cancers. It is possible that these could also be used to defend against Ebola virus.
Jim Kelly | EurekAlert!
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Information Technology
17.07.2018 | Materials Sciences
17.07.2018 | Power and Electrical Engineering