Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Juvenile diarrhea virus analyzed

19.07.2011
Rice University scientists define structure of astrovirus

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."

The capsid is a hard shell 33 nanometers wide that contains and protects its RNA. It has 30 even tinier spikes projecting from the surface, and each of those spikes may have a receptor-binding site.

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!
Further information:
http://www.rice.edu

Further reports about: RNA Science TV atomic structure human cell immune system juvenile

More articles from Life Sciences:

nachricht Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory

nachricht ‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

Im Focus: A transistor of graphene nanoribbons

Transistors based on carbon nanostructures: what sounds like a futuristic dream could be reality in just a few years' time. An international research team working with Empa has now succeeded in producing nanotransistors from graphene ribbons that are only a few atoms wide, as reported in the current issue of the trade journal "Nature Communications."

Graphene ribbons that are only a few atoms wide, so-called graphene nanoribbons, have special electrical properties that make them promising candidates for the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

Blockchain is becoming more important in the energy market

05.12.2017 | Event News

 
Latest News

Making fuel out of thick air

08.12.2017 | Life Sciences

Rules for superconductivity mirrored in 'excitonic insulator'

08.12.2017 | Information Technology

Smartphone case offers blood glucose monitoring on the go

08.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>