Biologists have long wondered if mammals share the elegant system used by insects, bacteria and other invertebrates to defend against viral infection. Two back-to-back studies in the journal Science last year said the answer is yes, but a study just published in Cell Reports by researchers at the Icahn School of Medicine at Mount Sinai found the opposite.
In the Mount Sinai study, the results found that the defense system used by invertebrates — RNA interferences or RNAi — is not used by mammals as some had argued. RNAi are small molecules that attach to molecular scissors used by invertebrates to cut up invading viruses.
Mammals use a form of RNAi to fine-tune the expression of hundreds of genes that coordinate development in the womb, says the study's senior author, Benjamin tenOever, PhD, Fishberg Professor in the Department of Medicine and Department of Microbiology at the Icahn School of Medicine at Mount Sinai. But it has never been clear that adult mammals use RNAi the same way that plants and insects do, he says. "Mammals have cell machinery that looks capable of producing RNAi to fight virus, but we believe it only helps to produce different small RNA products called microRNAs, which are not antiviral," Dr. tenOever says.
The correct answer matters because RNAi is being studied as a potential basis for new kinds of drugs for the treatment of hemophilia, beta-thalassemia and many viral infections, says Dr. tenOever.
"We believe our results settle a longstanding debate about whether mammals, including humans and mice, fight viruses using RNAi, and the answer is good news," he says. "Drug designers interested in using RNAi to treat disease have worried that if RNAi is part of the mammalian response to viral infections, RNAi-based agents could compromise a human's immune response, producing unintended consequences. That is not a concern now, based on our findings."
Mammals are known to fend off viruses with a system based on interferons, signaling proteins made by immune cells that amplify the body's attack on invaders. The finding that mammals do not use RNAi to fight viruses suggests that RNAi-based drugs could augment the existing interferon response in mammals, Dr. tenOever says. "We could harness this potent RNAi viral-killing machine when natural human immunity isn't enough."
To answer the question, a team of researchers from the Icahn Graduate School of Biomedical Science used a virus that produces oral lesions in cows and pigs. They eliminated the part of the virus that causes disease, rendering it harmless and susceptible to both RNAi and interferons. They then took this harmless virus and gave it the capacity to block either interferon or RNAi.
In experiments with mice, when the virus was designed to block interferon, no immune defense occurred and the interferon-blocking virus flourished. In contrast, giving the virus the capacity to block RNAi, found that the animals mounted a robust interferon-based defense that further weakened the RNAi-blocking virus. The same thing happened when the RNAi-blocking virus was introduced to engineered mice that could not produce interferons. "If mammals used interferon and RNAi to fight the virus, we would have seen the RNAi-blocking virus flourish in at least this setting — but we did not," Dr. tenOever says. "This is the strongest published data that argues against recent claims that RNAi exists in mammals, he says.
Study co-authors include Mount Sinai researchers Simone Backes, PhD, Ryan Langlois, PhD, Sonja Schmid, PhD, Andrew Varble, PhD, Jaehee Shim and David Sachs. The study was supported in part by the U.S. Army Research Laboratory and the U.S. Army Research Office under grant numbers W911NF-12-R-0012 and W911NF-07-R-0003.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community‐based facilities to tertiary and quaternary care.
The System includes approximately 6,600 primary and specialty care physicians, 12‐minority‐owned free‐standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.
For more information, visit http://www.mountsinai.org, or find Mount Sinai on Facebook, Twitter and YouTube.
Greg Williams | Eurek Alert!
Cells migrate collectively by intermittent bursts of activity
30.09.2016 | Aalto University
The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!
30.09.2016 | CNRS (Délégation Paris Michel-Ange)
Heavy construction machinery is the focus of Oak Ridge National Laboratory’s latest advance in additive manufacturing research. With industry partners and university students, ORNL researchers are designing and producing the world’s first 3D printed excavator, a prototype that will leverage large-scale AM technologies and explore the feasibility of printing with metal alloys.
Increasing the size and speed of metal-based 3D printing techniques, using low-cost alloys like steel and aluminum, could create new industrial applications...
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.
Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...
Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.
Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
30.09.2016 | Event News
29.09.2016 | Event News
28.09.2016 | Event News
30.09.2016 | Materials Sciences
30.09.2016 | Earth Sciences
30.09.2016 | Life Sciences