Two domains or portions of the protein NS1 combine to form tiny tubules where double-stranded RNA is hidden from the immune system, said Dr. B. V. Venkataram Prasad, professor of biochemistry and molecular biology, molecular virology and microbiology at BCM and his student, Dr. Zachary A. Bornholdt (now of the Scripps Research Institute in La Jolla, California).
"Once we confirm the importance of this structural information, we should be able to design drugs to block this action," said Prasad. "There are other things the protein could do to interfere with different immune mechanisms. We don't know if this is the only mechanism or if there are others that also come into play during influenza virus infection."
The two researchers had already recognized the importance of the protein NS1 in the virulence of influenza viruses and particularly, H5N1, a form of avian flu associated with more than half the deaths in a 2004 "bird flu" outbreak that resulted in 50 human cases and 36 deaths in Vietnam, China and Thailand. In all but one case, experts ruled out human-to-human spread of the virus. In a previous report, Prasad and Bornholdt described the structure of an area of the protein called the effector domain. In this report, a series of elegant experiments designed and carried out over eight months by Bornholdt allowed the two scientists to "crystallize" the entire protein.
By doing this, they were able to determine its structure using a technique called X-ray crystallography. This technique enables scientists to determine the three-dimensional structure of proteins and other bio-molecules by scattering X-rays through a crystal of the molecule. They substantiated their structure with cryo-electron microscopy, which makes images of tiny frozen structures using an extremely powerful electron microscope.
That structure revealed a previously unsuspected idiosyncrasy of NS1 in H5N1 that could explain the virus' virulence. In most cases, when an infected cell is exposed to a virus, double-stranded RNA molecules are formed triggering a potent anti-viral response that involves production of interferon.
However, the two domains of NS1 in this H5N1 interact to form tiny tubules. The double-stranded RNA is hidden or sequestered in these structures. The cell never sees a significant length of the RNA and does not marshal its immune forces to the fight the virus. Prasad and Bornholdt believe also that cellular factor binding sites found on the surface of the tubules also play a role in fooling the immune system.
"This is only one structure," said Prasad. "We need to see if this holds up with other NS1 structures from other influenza viruses."
Bornholdt's technique for crystallizing the protein will prove valuable in pursuing this work, said Prasad.
"Is this a common mechanism for eluding the immune system?" he said. He said hopes to build a library to NS1 structures to facilitate future studies designed to fight influenza worldwide.
While H5N1 is not usually transmitted from human-to-human at this point, a small change in its genetic structure – perhaps an exchange of genes with a more easily transmitted flu virus – could change that, he said. Developing drugs to fight the virus could prove life-saving in a pandemic.
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Life Sciences
19.10.2017 | Interdisciplinary Research
19.10.2017 | Earth Sciences