A Massachusetts General Hospital (MGH)-led research team has identified an immune cell protein that is critical to setting off the body's initial response against viral infection.
The report that will be published in an upcoming issue of Nature Immunology and is receiving early online release describes finding that a protein called GEF-H1 is essential to the ability of macrophages – major contributors to the innate immune system – to respond to viral infections like influenza.
"The detection of viral genetic material inside an infected cell is critical to initiating the responses that signal the immune system to fight an infection and prevent its spread throughout the body," says Hans-Christian Reinecker, MD, of the Center for the Study of Inflammatory Bowel Disease in the MGH Gastrointestinal Unit, senior author of the report. "Our findings indicate that GEF-H1 may control immune responses against a wide variety of RNA and DNA viruses that pose a threat to human health."
The body's first line of defense against infection, the innate immune system rapidly responds to invading pathogens by mobilizing white blood cells, chemical factors called cytokines and antimicrobial peptides. When viruses invade cells, they often move towards the nucleus in order to replicate and sometimes to integrate their own genetic material into that of the host cell, traveling along structures called microtubules that cells use for internal protein transport. But how microtubule-based movement of viral components contributes to induction of the immune response has been unknown.
GEF-H1 is known to bind to microtubules, and previous research indicated that it has a role in immune recognition of bacteria. A series of experiments by Reinecker's team found that GEF-H1 is expressed in macrophages – key components of the innate immune system – and activated in response to viral RNA and that it controls the expression of beta interferon and other cytokines. Mice in which expression of GEF-H1 was knocked out were unable to mount an effective immune response to influenza A and to encephalomyocarditis, a virus that causes several types of infection in animals.
"The sensing of intracellular viral nucleic acids for induction of interferons is so important that many viruses, including influenza A, have evolved specific strategies to interfere with activation of the interferon defense system," says Reinecker, an associate professor of Medicine at Harvard Medical School. "We are hopeful that this discovery will allow the development of new strategies to curtail viral mechanisms that impede the immune responses to infections that are often associated with high mortality rates."
The co-lead authors of the Nature Immunology report are Hao-Sen Chiang, PhD, and Yun Zhao, MD, PhD, MGH Gastrointestinal Unit. Additional co-authors are Joo-Hye Song, PhD, Song Liu, MD, Megha Basavappa and Kate Jeffrey, PhD, MGH Gastrointestinal Unit; Ninghai Wang, MD, PhD, and Cox Terhorst, Beth Israel Deaconess Medical Center; and Arlene Sharpe, MD, PhD, Harvard Medical School. The study was supported by National Institutes of Health grants AI093588, DK-068181, DK-033506, 630 DK-043351 and DK-52510.
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $775 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences