(New York, NY - January 14, 2019) -- Herpes viral infections use the ancient genetic material found in the human genome to proliferate, mimicking the same process tumors have been found to manipulate, Mount Sinai researchers have shown for the first time. These observations provide further insight about how herpes viruses can manipulate the immune system in ways that may drive neurodegenerative diseases like Alzheimer's, according to the study, published in Nature Communications in January.
The researchers found that herpes viruses appear to manipulate an ancient RNA species that originated several million years ago, called human satellite II RNA (HSATII RNA). HSATII RNA is normally inactive, but both herpes viruses and cancer cells have essentially learned to activate it, using this RNA to manipulate their environment to help them invade the body and grow.
The researchers believe that both viruses and cancer cells figured out how to use this RNA because they both rapidly evolve to test out different strategies to multiply and spread within the body over time. Researchers have yet to understand whether herpes and cancer came upon this strategy coincidentally or whether they work hand in hand in some cases. Several researchers involved in this work pioneered the study of how a different type of RNA affects tumor evolution.
"The evolution of tumors can teach us about viruses and vice versa, and understanding one system may help us treat the other," said one of the study's senior authors, Benjamin Greenbaum, PhD, Assistant Professor of Oncological Sciences, Pathology, and Medicine (Hematology and Medical Oncology) at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "The HSATII RNA induction seen in herpes infections and cancer cells suggests possible convergence upon common mechanisms in these seemingly disparate diseases."
The study potentially gives further insight into how herpes viruses might play a role in developing colitis and neurodegenerative diseases like Alzheimer's. It is the first step toward potentially developing diagnostic tools that look for these types of RNAs in cancer and herpes patients and using the ancient RNAs as targets for drugs in the future, said Dr. Greenbaum.
The lead author of the study was Maciej Nogalski, PhD, Postdoctoral Research Fellow in the laboratory of co-senior author Thomas Shenk, PhD, James A. Elkins Professor of Life Sciences in the Department of Molecular Biology at Princeton University.
"Herpes viruses have been extensively studied for many years, but once again by investigating host-virus interactions at the cellular level we were privileged to get insights into novel regulatory mechanisms of human cells. Our virus-centered studies not only uncovered interesting aspects of viral infection, but also provided an inducible system that could accelerate investigations about possible roles HSATII RNA plays in other diseases," Dr. Nogalski says.
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Researchers from Massachusetts General Hospital and the Simons Center for Systems Biology at the Institute for Advanced Study also contributed to this work. This research received funding from the National Institutes of Health (AI112951), the American Cancer Society(PF-14-116-01 MPC), the V Foundation, Stand Up to Cancer, the National Science Foundation, and the Lustgarten Foundation, the Pershing Square Sohn Research Alliance, the Mark Foundation, the Burroughs Wellcome Fund, and Affymetrix, Inc.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system encompassing (with the addition of South Nassau Communities Hospital) eight hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.
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Journal
Nature Communications