Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Viral infections: Identifying the tell-tale patterns


LMU researchers have identified the structural features that enable the innate immune system to discriminate between viral and endogenous RNAs in living cells.

When viruses infect cells, they take control of cellular metabolism and hijack cellular resources for the production of viral proteins. This process is dependent on viral RNA molecules that are delivered directly to (in the case of RNA viruses) and/or newly synthesized in the host cell, and provide the blueprints for the fabrication of viral proteins by the cell’s translational apparatus.

Interaction profiles of cellular RNA sensors with RNA strands of the measles virus genome (superimposed on a micrograph showing cells infected with measles virus).

However, cells possess defense systems that are activated by specialized sensors that can distinguish viral RNAs from host RNAs. These proteins, three of which belong to the family of RIG-I like receptors (or RLRs), recognize and bind specifically to foreign RNAs. This in turn alerts the innate immune system, which proceeds to destroy the foreign RNAs, thus preventing the production of new virus particles.

“Based on in-vitro experiments, it is known that RLR proteins bind to certain characteristic patterns in viral RNAs, but it had not been possible to isolate the precise RNA sequences bound by these proteins in living, virus-infected cells,” says Professor Karl-Peter Hopfner of LMU’s Genzentrum.

... more about:
»DNA »LMU »MDA5 »RIG-I »RNA »RNAs »composition »diseases »mechanisms »protein »proteins

Tethering RNA to proteins with UV light

Hopfner, in collaboration with his colleagues Karl-Klaus Conzelmann (LMU), Johannes Söding (LMU) and Adolfo García-Sastre (Mount Sinai Hospital, New York), made use of a clever experimental strategy to get around this problem, which enabled them to purify and characterize ribonucleoprotein complexes containing viral RNAs from virus-infected cells.

The intrinsic stability of the interaction between RLRs and viral RNAs is very low. So the researchers first had to stabilize the complexes in order to isolate them intact. For this purpose, they infected cells with measles virus, and incubated them in the presence of a chemically modified, photo­activatable RNA precursor, which is incorporated into newly synthesized viral RNAs. “Provided that the physical distance between an RNA and its binding protein is short enough, subsequent exposure of such cells to UV light induces the formation of a stable covalent bond between them,” Hopfner explains.

The resulting RNA-protein complexes could then be isolated from the cells and, after detachment of the proteins, the nucleotide sequences of the RNAs could be determined. “This allowed us to determine how RLRs recognize foreign RNAs and how the latter differ from endogenous cellular RNAs,” says Hopfner.

The researchers found that the RLR proteins RIG-I and MDA5 indeed recognize defined elements within viral RNAs in living cells that have been infected by measles virus. Like many other viruses, including the one that causes rabies, the measles virus possesses a single-stranded RNA genome. Unlike DNA viruses, it therefore delivers an RNA template directly into the host cell. However, this molecule must then be transcribed by its associated viral RNA polymerase to generate the mRNAs required for synthesis of viral proteins and propagation of the infection.

Sensors bind to specific regions

“And while RIG-I preferentially binds to certain sequence patterns found at the exposed ends of different viral RNAs both in vitro and in vivo, MDA5 rather surprisingly recognizes not the viral genome itself, but apparently certain regions located within viral mRNAs,” Hopfner explains. Moreover, these regions differ in their base composition from sequences found in other viral RNAs, suggesting that MDA5 relies on these structural differences to discriminate between viral and endogenous RNAs.

Hopfner and his team now plan to investigate the interaction of RLRs with other viral nucleic acids, in order to obtain a clearer picture of the molecular mechanisms that enable these proteins to detect foreign RNAs. This should in turn shed light on why the innate immune system has difficulty in responding to particular viruses, and how RLR-associated autoimmune diseases such as rheumatoid arthritis arise. A better understanding of both of these issues could suggest new approaches to the treatment of both viral infections and autoimmunity.
(PloS Pathogens 2014)       

Luise Dirscherl | Eurek Alert!
Further information:

Further reports about: DNA LMU MDA5 RIG-I RNA RNAs composition diseases mechanisms protein proteins

More articles from Life Sciences:

nachricht Understanding a missing link in how antidepressants work
25.11.2015 | Max Planck Institute of Psychiatry, München

nachricht Plant Defense as a Biotech Tool
25.11.2015 | Austrian Centre of Industrial Biotechnology (ACIB)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Innovative Photovoltaics – from the Lab to the Façade

Fraunhofer ISE Demonstrates New Cell and Module Technologies on its Outer Building Façade

The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...

Im Focus: Lactate for Brain Energy

Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.

In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...

Im Focus: Laser process simulation available as app for first time

In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.

Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...

Im Focus: Quantum Simulation: A Better Understanding of Magnetism

Heidelberg physicists use ultracold atoms to imitate the behaviour of electrons in a solid

Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...

Im Focus: Climate Change: Warm water is mixing up life in the Arctic

AWI researchers’ unique 15-year observation series reveals how sensitive marine ecosystems in polar regions are to change

The warming of arctic waters in the wake of climate change is likely to produce radical changes in the marine habitats of the High North. This is indicated by...

All Focus news of the innovation-report >>>



Event News

Fraunhofer’s Urban Futures Conference: 2 days in the city of the future

25.11.2015 | Event News

Gluten oder nicht Gluten? Überempfindlichkeit auf Weizen kann unterschiedliche Ursachen haben

17.11.2015 | Event News

Art Collection Deutsche Börse zeigt Ausstellung „Traces of Disorder“

21.10.2015 | Event News

Latest News

Harnessing a peptide holds promise for increasing crop yields without more fertilizer

25.11.2015 | Agricultural and Forestry Science

Earth's magnetic field is not about to flip

25.11.2015 | Earth Sciences

Tracking down the 'missing' carbon from the Martian atmosphere

25.11.2015 | Physics and Astronomy

More VideoLinks >>>