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 Matabele ants: Travelling faster with detours
21.05.2018 | Julius-Maximilians-Universität Würzburg

nachricht Asian tiger mosquito on the move
20.05.2018 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>