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 Nerve cells with a sense of rhythm
25.08.2016 | Deutsches Primatenzentrum GmbH - Leibniz-Institut für Primatenforschung

nachricht Genetic Regulation of the Thymus Function Identified
23.08.2016 | 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: Streamlining accelerated computing for industry

PyFR code combines high accuracy with flexibility to resolve unsteady turbulence problems

Scientists and engineers striving to create the next machine-age marvel--whether it be a more aerodynamic rocket, a faster race car, or a higher-efficiency jet...

Im Focus: X-ray optics on a chip

Waveguides are widely used for filtering, confining, guiding, coupling or splitting beams of visible light. However, creating waveguides that could do the same for X-rays has posed tremendous challenges in fabrication, so they are still only in an early stage of development.

In the latest issue of Acta Crystallographica Section A: Foundations and Advances , Sarah Hoffmann-Urlaub and Tim Salditt report the fabrication and testing of...

Im Focus: Piggyback battery for microchips: TU Graz researchers develop new battery concept

Electrochemists at TU Graz have managed to use monocrystalline semiconductor silicon as an active storage electrode in lithium batteries. This enables an integrated power supply to be made for microchips with a rechargeable battery.

Small electrical gadgets, such as mobile phones, tablets or notebooks, are indispensable accompaniments of everyday life. Integrated circuits in the interiors...

Im Focus: UCI physicists confirm possible discovery of fifth force of nature

Light particle could be key to understanding dark matter in universe

Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according...

Im Focus: Wi-fi from lasers

White light from lasers demonstrates data speeds of up to 2 GB/s

A nanocrystalline material that rapidly makes white light out of blue light has been developed by KAUST researchers.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The energy transition is not possible without Geotechnics

25.08.2016 | Event News

New Ideas for the Shipping Industry

24.08.2016 | Event News

A week of excellence: 22 of the world’s best computer scientists and mathematicians in Heidelberg

12.08.2016 | Event News

 
Latest News

Spherical tokamak as model for next steps in fusion energy

25.08.2016 | Power and Electrical Engineering

Scientists identify spark plug that ignites nerve cell demise in ALS

25.08.2016 | Health and Medicine

Secure networks for the Internet of the future

25.08.2016 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>