Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Purdue biologists expose the inner workings of viral machine

16.12.2003


Purdue University scientists have peered inside a virus and visualized for the first time how it produces and exports genetic materials into a host cell, an advance in fundamental research that also could have implications for the development of antiviral agents.


This cross section of a reovirus shows features down to 7.6-angstrom resolution, a scale that has allowed Purdue University’s Tim Baker and his research team to examine the inner features of the viral particle. Visible for the first time within the virus are several tiny "factories," shown here in red, which convert raw materials from a victim cell’s interior into RNA messages instructing the cell to begin manufacturing more viruses. The technology Baker’s team used to examine the reovirus could be used to reveal other viruses’ structures, providing fundamental knowledge important for developing potential antiviral agents. (Photo by Purdue University/Department of Biology)



Using improved microscope technology, a team including Purdue’s Timothy S. Baker and a colleague at Harvard has determined the structure of a reovirus (short for "respiratory enteric orphan" virus) down to the 7.6-angstrom scale, better than twice the 18-angstrom resolution previously available. The newly obtained structure shows not only the molecular composition of the virus but even the position and orientation of those molecules.

"We have visualized the innards of a human reovirus at an unprecedentedly high resolution," said Baker, who is professor of biology in Purdue’s School of Science. "We can now look at the components of the viral machine to see how they work, which hopefully will give us insight into how it manufactures the genetic weapons it uses to infect cells."


The reovirus is a member of a viral family that often causes diarrhea in young children. Infections caused by the closely related rotaviruses, for example, are responsible for approximately 1 million deaths annually in developing countries where water shortages can make rehydration difficult for victims.

The research, which appears in the December issue of "Nature Structural Biology," was performed by a team of Purdue researchers, including first author and graduate student Xing (pronounced SHING) Zhang, graduate student Steve Walker, and cryo-microscopist Paul Chipman. The work is part of a long-standing collaborative study of reoviruses with Max L. Nibert of Harvard Medical School’s Department of Microbiology and Molecular Genetics.

Reoviruses are members of an unusual viral family, in that they do not simply deposit their genetic material into the victim’s cytoplasm, or interior, in order to create new virus particles. Most viruses can do so with relative impunity, but reovirus RNA has a double-stranded structure that a host could perceive as a threat. RNA is a molecule closely related to DNA and exists in a form known as the "messenger molecule" that leads to the translation of genetic information within cells.

"If a reovirus exposed its strands of RNA to a cell’s cytoplasm directly, the cell’s defense mechanisms would destroy them before they could multiply," Baker said. "So once a reovirus particle invades a cell, it doesn’t open up like other ‘Trojan horse’ viruses do. Instead, it keeps its ‘troops’ inside, where it takes raw materials from the cytoplasm. From them, it manufactures single-stranded RNA instructions that order the cell to transform itself into a virus-producing factory."

These single strands of RNA are assembled within the virus in part by a protein molecule called lambda-3 that operates somewhat like a printing press. The raw materials are drawn like blank paper through a hole in the protein, which also contains a loop of the virus’ double-stranded RNA. Like a printing cylinder that contains a master copy of a book’s page, the protein uses the viral RNA loop again and again to generate single-stranded RNA messages from the raw materials. The single strands, which can go unrecognized as a threat by the victim cell’s defenses, spew out of the virus into the cytoplasm like pages off a printing press.

"It is this single-stranded RNA that instructs the cell to begin manufacturing new viruses," Baker said. "Our research has essentially determined the position and orientation of lambda-3 ‘presses’ within the virus that print it. We thus have a much clearer understanding of the internal workings of the reovirus machine now – understanding that could play a role in determining how to stop those presses someday."

The discovery was possible because of an innovative improvement on the microscope technology developed in Baker’s lab at Purdue. To get the complete image, graduate student Zhang obtained images of 8,000 different particles, each of which showed a viral particle from a slightly different orientation. With the help of the improved technology, he obtained the precise orientation for each particle and then superimposed them to obtain a single, three-dimensional map with all the particle’s features visible.

"From any one vantage point, only part of the virus is visible clearly," Zhang said. "But with enough images, it was possible to assemble them into a coherent, complete picture."

While Baker is optimistic that the technique can be applied to many different viruses, he said at this point it is limited primarily to the study of symmetric viruses.

"Reoviruses are highly regular, with little differentiation between one particle and another," Baker said. "However, many viruses, such as HIV, are polymorphic, meaning each particle is asymmetric and differs slightly from its kin. At this point, we unfortunately cannot look at polymorphic viruses at high resolution with current technology."

Nonetheless, the technique does permit detailed examination of other components of symmetric viruses, such as the proteins in the virus’ capsid, or outer shell.

"Zhang is now studying one of the capsid proteins in greater detail," Baker said. "At resolution of 7 angstroms or better, it might eventually help scientists figure out how to develop an effective antiviral to stop the process."

With modifications, the viral particles might be used to treat other diseases.

"Someday, scientists might be able to change the virus to custom manufacture RNA that sends messages we choose," Baker said. "We could use it to fight other viral infections or potentially even cancer."

Baker’s team is associated with several interdisciplinary centers at Purdue, including the Markey Center for Structural Biology and the Purdue Cancer Center.

Funding for this research was provided in part by a grant from the National Institutes of Health and a Keck Foundation award.

Writer: Chad Boutin, (765) 494-2081, cboutin@purdue.edu
Sources: Tim Baker, (765) 494-5645, tsb@bilbo.bio.purdue.edu
Xing Zhang, (765) 494-8172, zhangx@bilbo.bio.purdue.edu
Purdue News Service: (765) 494-2096; purduenews@purdue.edu

Chad Boutin | Purdue News
Further information:
http://news.uns.purdue.edu/html4ever/031215.Baker.reovirus.html
http://www.nature.com/cgitaf/DynaPage.taf?file=/nsb/journal/v10/n12/full/nsb1009.html

More articles from Life Sciences:

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

nachricht Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers create artificial materials atom-by-atom

28.03.2017 | Physics and Astronomy

Researchers show p300 protein may suppress leukemia in MDS patients

28.03.2017 | Health and Medicine

Asian dust providing key nutrients for California's giant sequoias

28.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>