Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Viral infections: Identifying the tell-tale patterns

24.04.2014

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:
http://www.en.uni-muenchen.de/news/newsarchiv/2014/hopfner_infektion.html

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

More articles from Life Sciences:

nachricht A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory

nachricht A New Discovery in the Fight against Cancer: Tumor Cells Switch to a Different Mode
29.04.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

Im Focus: Ultra-thin glass is up and coming

As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.

Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Winds a quarter the speed of light spotted leaving mysterious binary systems

29.04.2016 | Physics and Astronomy

Fiber optic biosensor-integrated microfluidic chip to detect glucose levels

29.04.2016 | Health and Medicine

A cell senses its own curves: New research from the MBL Whitman Center

29.04.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>