Rice University scientists have defined the structure -- down to the atomic level -- of a virus that causes juvenile diarrhea. The research may help direct efforts to develop medications that block the virus before it becomes infectious.
The new paper by Professor Yizhi Jane Tao, postdoctoral researcher Jinhui Dong and their colleagues was published in today's online edition of the Proceedings of the National Academy of Sciences.
Tao's Rice lab specializes in gleaning fine details of viral structures through X-ray crystallography and computer analysis of the complex molecules, ultimately pinpointing the location of every atom. That helps researchers see microscopic features on a virus, like the spot that allows it to bind to a cell or sites that are recognized by neutralization antibodies.
Among four small RNA viruses that typically infect people and animals, Tao said, astrovirus was the only one whose atomic structure was not yet known. First visualized through electron microscopy in 1975, it became clear in subsequent studies that the virus played a role in juvenile -- and sometimes adult -- outbreaks of diarrhea, as the second leading cause after rotavirus. Passed orally, most often through fecal matter, the illness is more inconvenient than dangerous, but if left untreated, children can become dehydrated.
The virus works its foul magic in humans' lower intestines, but to get there it has to run a gauntlet through the digestive tract and avoid proteases, part of the human immune system whose job is to destroy it. (Though one, trypsin, actually plays a role in activating astrovirus, she said.) When the astrovirus finds a target and viral RNA is let loose inside human cells, virus replication starts. If the host's immune system does not do a good enough job in removing the viruses, the malady will run its uncomfortable course in a couple of days.Astrovirus bears a strong resemblance to the virus that causes hepatitis E (HEV). Tao, an associate professor of biochemistry and cell biology, said she decided to investigate astrovirus after completing a similar study of HEV two years ago. "I was thinking there's some connection between those viruses," she said. "Based on that assumption, we started to make constructs to see if we could produce, to start with, the surface spike on the viral capsid."
Once the atomic structure of the spike was known, finding the receptor site took detective work that involved comparing genomic sequences of eight variants of astrovirus to find which were the best conserved. "Among those eight serotypes, we figured there must be a common receptor, and that should be conserved on the surface," said Dong, the paper's lead author.
In looking for the common receptor, the team found a shallow pocket in the spike that became a prime suspect for receptor binding.
The researchers also discovered the astrovirus may have a sweet tooth. "The size of the pockets suggests that it would most likely bind to sugar molecules, like disaccharides or trisaccharides," Tao said. "It may be that the virus binds to the sugar molecule and that helps it bind to the surface of a target cell."
Finally, the team also determined astrovirus resembles another of the four types of RNA-based viruses, calicivirus, although more remotely than HEV. They suspect astrovirus may be a hybrid, with parts derived from both HEV and calicivirus. "Clearly, these three are related somehow. It's an interesting point, but we can't determine that relationship based on what we know right now."
What researchers can do is begin to develop a vaccine or antiviral drug that will block astrovirus. "There's already a phase II vaccine (in trials) for HEV, so that gives us hope," Dong said.
"We will certainly work with other labs to identify compounds that can bind to this potential pocket," Tao said. "We can do this computationally. We can screen 50,000 compounds, for example, to see which may bind to the protein with high affinity. Then we can start the optimization procedure."
Co-authors of the paper are former Rice graduate student Liping Dong and Ernesto Méndez, a researcher at the National Autonomous University of Mexico.
The Welch Foundation, the National Institutes of Health and the Kresge Science Initiative Endowment Fund supported the research.
Jade Boyd | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy