Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Reveal a New Way Viruses Cause Cells to Self-Destruct

19.11.2002


Scientists at the U.S. Department of Energy’s Brookhaven National Laboratory and their collaborators have discovered that some viruses can use the most abundant protein in the cells they are infecting to destroy the cells and allow new viruses to escape to infect others. The findings, described in the November 29, 2002, issue of the Journal of Biological Chemistry, build upon earlier Brookhaven research on how virus particles become infectious (see related story) and may lead to the design of more effective antiviral remedies.


This ribbon diagram is a theoretical representation of the structure of adenovirus protease (red) bound to the cytoskeleton protein actin (green). The blue, green, and yellow balls show the location of the active site of the adenovirus protease.


The same two cells were photographed to show the location of the adenovirus protease (labeled with a green fluorescent molecule) and the cytoskeleton protein cytokeratin 18 (labeled with a red fluorescent molecule). The adenovirus protease is known to cleave cytokeratin 18 (as well as other cytoskeletal proteins), and this experiment shows they are located at the same sites within the cells.



"This is a new and philosophically interesting way for a virus to escape from cells," said Brookhaven biologist Walter Mangel, a coauthor on the paper. "In essence, a protein in the infected cells can serve as the seed of the cells’ own destruction."

Mangel’s group has previously shown that adenovirus -- a virus that causes respiratory and gastrointestinal infections and also conjunctivitis -- produces a protein-cleaving enzyme, or protease, to complete the maturation of newly synthesized virus particles. Similar to the way supportive scaffolding is removed after the completion of a construction project, this protease cleaves, or cuts out, viral "construction" proteins, leaving infectious virus particles behind.


This viral protease is produced in the cytoplasm in an inactive form, and must migrate to the nucleus to become activated in newly synthesized viral particles by two viral cofactors. Once activated, it can cleave several viral proteins to complete the viral maturation process. There were no indications that the protease could be activated in the cell’s cytoplasm.

When Mangel presented this research at a seminar at Princeton University, Clarence Schutt, a Princeton chemistry professor, pointed out that the amino acid sequence of one of the viral cofactors was dramatically similar to the sequence of actin, a cytoplasmic protein that gives shape and structure to cells. Mangel wondered if actin could activate the protease, and took some from Schutt’s lab back to Brookhaven to do the experiment.

The result: Incubating actin and the adenovirus protease increased the cleaving ability of the protease, just like the viral cofactor did, allowing the actin-protease complex to cleave actin itself, as well as other cellular skeleton proteins.

"When actin and other cytoskeleton proteins are destroyed," Mangel explained, "a cell loses its shape and eventually breaks open, allowing the newly synthesized virus particles to escape and infect other cells."

While other viruses are known to cleave actin and other cytoskeleton proteins as a means of breaking free to continue infection, none of them is known to use actin as a cofactor in this process, Mangel said. "Thus, the really interesting finding in this case is that actin is a cofactor for its own destruction," Mangel said.

The next step for Mangel’s group will be to crystallize complexes of actin bound to the adenovirus protease to determine its atomic structure at the National Synchrotron Light Source at Brookhaven.

"The structure would then be used to find drugs to prevent the interaction between actin and the adenovirus protease," Mangel said. "Such drugs could serve as a new type of antiviral agent."

This work was done in collaboration with Mark Brown, Kevin McBride, Mary Lynn Baniecki, and Nancy Reich of Stony Brook University and Gerard Marriott of the University of Wisconsin. It was funded by the U.S. Department of Energy, which supports basic research in a variety of scientific fields, and the National Institutes of Health.

Karen McNulty Walsh, | Brookhaven National Laboratory
Further information:
http://www.bnl.gov/bnlweb/pubaf/pr/2002/bnlpr111902.htm

More articles from Life Sciences:

nachricht New switch decides between genome repair and death of cells
27.09.2016 | University of Cologne - Universität zu Köln

nachricht A blue stoplight to prevent runaway photosynthesis
27.09.2016 | National Institute for Basic Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Laser use for neurosurgery and biofabrication - LaserForum 2016 focuses on medical technology

27.09.2016 | Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

 
Latest News

New switch decides between genome repair and death of cells

27.09.2016 | Life Sciences

Nanotechnology for energy materials: Electrodes like leaf veins

27.09.2016 | Physics and Astronomy

‘Missing link’ found in the development of bioelectronic medicines

27.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>