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!
Atom-Sized Craters Make a Catalyst Much More Active
30.11.2015 | SLAC National Accelerator Laboratory
Hydra Can Modify Its Genetic Program
30.11.2015 | Université de Genève (University of Geneva)
Before the fluid of the middle ear drains and sound waves penetrate for the first time, the inner ear cells of newborn rodents practice for their big debut. Researchers at Johns Hopkins report they have figured out the molecular chain of events that enables the cells to make “sounds” on their own, essentially “practicing” their ability to process sounds in the world around them.
The researchers, who describe their experiments in the Dec. 3 edition of the journal Cell, show how hair cells in the inner ear can be activated in the absence...
Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.
Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...
The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
30.11.2015 | Event News
25.11.2015 | Event News
17.11.2015 | Event News
30.11.2015 | Trade Fair News
30.11.2015 | Trade Fair News
30.11.2015 | Trade Fair News