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
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
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...
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...
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...
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...
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...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction