Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team learns how cellular protein detects viruses and sparks immune response

23.02.2009
A study led by researchers at the University of Illinois reveals how a cellular protein recognizes an invading virus and alerts the body to the infection.

The research, described this week in the journal Science and led by Illinois physics professor and Howard Hughes Medical Institute investigator Taekjip Ha, settles a debate over how the protein, RIG-I (pronounced rig-EYE), is able to distinguish between viral RNA and self (or cellular) RNA.

"RIG-I is the first molecule in the immune response to detect viral RNA," said Sua Myong, lead author on the study and a professor at the U. of I.'s Institute for Genomic Biology. Unlike most other proteins known to detect viral infections only in specialized immune cells, RIG-I is active in every cell type in the body, she said.

The RIG-I protein has two major parts: caspase-recruitment domains (CARDs) and an ATPase domain that consumes ATP, the cellular fuel molecule.

Previous studies had shown that the CARD domains actually inhibit the activity of RIG-I when no virus is present, but are vital to sounding the alarm and triggering an immune response once a certain type of virus has been detected.

Other studies had found that RIG-I recognizes an important feature of viral RNAs that is missing from most human RNAs. This feature, a "triphosphate" tag at a particular end, the "five-prime" (5') end, of viral RNA, is a viral fingerprint that tells RIG-I that something is amiss. Detection of this tag starts a cascade of reactions that allows RIG-I to broadcast a message to other cellular components, and ultimately to other cells.

The researchers also knew that RIG-I was usually active in the presence of double-stranded RNA, not the single-stranded RNA found in most animal cells.

Earlier research had also shown that the central ATPase domain is critical to the function of the molecule. A single mutation in this region shuts down its activity altogether.

"We knew that the CARD domain was responsible for transmitting the antiviral signaling," Myong said. "And we knew how the 5'-triphosphate tag is detected. But a big question remained about the ATPase domain: It was using ATP to do something – but what?"

To solve that mystery, the researchers used a technique termed "protein-induced fluorescent enhancement." This method makes use of a fluorescent dye that, when attached to a specific region of a molecule such as RNA, glows with more or less intensity depending on its proximity to a protein that is interacting with that molecule.

Using this technique, the researchers found that the RIG-I protein moves back and forth (translocates) selectively on double-stranded RNA, and that this activity is greatly stimulated in the presence of 5'-triphosphate.

By requiring both the 5'-triphosphate and the double-stranded RNA for it to function, the RIG-I protein is able to very accurately detect a viral invader, said Ha.

Most cellular RNAs have their triphosphate tails bobbed, capped or otherwise modified before circulating in the cytosol of the cell, he said. "So this is one powerful way of distinguishing viral RNA from cellular RNA."

Prior to this study, researchers did not know if RIG-I sensed both the double-stranded RNA and the 5'-triphosphate separately, or in an integrated manner, said Myong.

"Our work bridges the gap," she said. "We show that it does both in an integrated manner."

Diana Yates | EurekAlert!
Further information:
http://www.illinois.edu

More articles from Studies and Analyses:

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

nachricht Urbanization to convert 300,000 km2 of prime croplands
27.12.2016 | Mercator Research Institute on Global Commons and Climate Change (MCC) gGmbH

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>