Our immunosensory system detects virus such as influenza via specific characteristics of viral ribonucleic acid.
Previously, it was unclear how the immune system prevents viruses from simply donning molecular camouflage in order to escape detection. An international team of researchers from the University of Bonn Hospital and the London Research Institute have now discovered that our immunosensory system attacks viruses on a molecular level. In this way, a healthy organism can keep rotaviruses, a common cause of diarrheal epidemics, at bay. The results have been published in the renowned journal "Nature".
Marion Goldeck, Dr. Martin Schlee (sitting), Dr. Winfried Barchet, Thomas Zillinger and Prof. Dr. med. Gunther Hartmann, Director of the Institute of Clinical Chemistry and Clinical Pharmacology.
(c) Photo: Claudia Siebenhüner/UKB
Every day our bodies are confronted with a variety of viruses and other pathogens. Our immune systems must constantly decide what is "foreign" and what is part of the body itself so that the body's own cells are not inadvertently attacked by its own defense troops. Viruses imitate the body's own structures and thus represent a special challenge for the immune system.
In this way, the immune system works like a sensory organ which continuously detects dangers and initiates the appropriate defense mechanisms. This immunosensory system searches for viruses by surveilling the body's own ribonucleic acid (RNA) for RNA with characteristics typical of viruses. In RNA viruses, RNA is the carrier of the virus's genetic information. To reproduce, viruses must multiply their RNA, and this multiplication leads to the development of molecular patterns which are in turn used to detect the viruses themselves.
It has been known for some time that RIG-I-like receptors (RLRs) play a crucial role in the detection of RNA viruses. These receptors act as “fire alarms” within the immune system: When RNA molecules from viruses bind to these receptors, a signal chain is initiated that leads to the production of substances that can ultimately combat the viruses.
"During amplification of viral RNA, a so-called triphosphate group, consisting of three phosphates, inevitably develops at one end of the newly formed RNA. A few years ago, we were the first to show that it is this triphosphate group which allows RIG-I to detect newly formed viral RNA. Previously, it was believed that viruses can elude this detection via simple deceptive molecular maneuvers," said Prof. Gunther Hartmann, Director of the Institute of Clinical Chemistry and Clinical Pharmacology of the University of Bonn Hospital.
RIG-I: A molecular attack against viruses
Together with scientists from the Immunobiology Laboratory of the London Research Institute in England, the scientists working with Dr. Martin Schlee and Prof. Dr. Gunther Hartmann at the University of Bonn Hospital investigated the immunorecognition of reoviruses. This family includes rotaviruses, which cause serious diarrheal illness and are responsible for the deaths of more than a million children worldwide every year.
The immunorecognition of reoviruses was previously unclear since their RNA does not contain a triphosphate group. Now the researchers discovered that, surprisingly, an RNA structure with two phosphates at the end of the RNA double-strand in reoviruses can likewise trigger RIG-I and alarm the immune system.
"This finding has significance for the detection of RNA viruses that extends far beyond reoviruses: It is comparatively simple for a virus to molecularly change the triphosphate in the course of its development,” said Dr. Schlee. The first step in this process is generally to split off the outermost phosphate of the triphosphate group, which leads to a diphosphate. This step is necessary for the virus to perform further modifications to its RNA and thus don a molecular cloak of invisibility.
However, any form of further molecular camouflage is made extremely difficult for the virus due to the additional highly specialized RIG-I-mediated immunorecognition of the diphosphate. Thus, RIG-I attacks the virus on both fronts, significantly restricting its further development.
"Without the investigation into reoviruses, we would not have discovered this universal mechanism of virus detection," said Prof. Hartmann. Since members of the reovirus family also contain a diphosphate group in their viral RNA, a healthy organism can also detect these viruses and curb these illnesses within a few days. However, malnourished children cannot summon these reserves, and the illness can become life-threatening.
The immune system: a sensory system for health
The researchers see a major application potential in the decoding of virus detection: "We are already currently developing artificially produced copies of viral RNA in order to alert our immune system to viruses in a targeted fashion," said Prof. Hartmann who is also director of the project "Novel Anti-infective Agents" at the German Centre for Infection Research (DZIF). Prof Hartmann is also currently speaker of the Cluster of Excellence ImmunoSensation, which is supported by a 28-million Euro grant from the German Research Foundation (DFG). The Cluster brings together experts from a variety of disciplines at the site and connects them to international research structures.
Publication: Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5’diphosphates, “Nature”, DOI: 10.1038/nature13590
Prof. Dr. med. Gunther Hartmann
Director of the Institute of Clinical Chemistry
and Clinical Pharmacology
of the University of Bonn Hospital
Johannes Seiler | idw - Informationsdienst Wissenschaft
High-arctic butterflies shrink with rising temperatures
07.10.2015 | Aarhus University
Long-term contraception in a single shot
07.10.2015 | California Institute of Technology
The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.
As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...
Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.
Inspired by insects
An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...
At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...
In cooperation with the Center for Nano-Optics of Georgia State University in Atlanta (USA), scientists of the Laboratory for Attosecond Physics of the Max Planck Institute of Quantum Optics and the Ludwig-Maximilians-Universität have made simulations of the processes that happen when a layer of carbon atoms is irradiated with strong laser light.
Electrons hit by strong laser pulses change their location on ultrashort timescales, i.e. within a couple of attoseconds (1 as = 10 to the minus 18 sec). In...
01.10.2015 | Event News
30.09.2015 | Event News
17.09.2015 | Event News
07.10.2015 | Medical Engineering
07.10.2015 | Power and Electrical Engineering
07.10.2015 | Earth Sciences