Mount Sinai Researchers Identify Vulnerabilities of the Deadly Ebola Virus
Disabling a protein in Ebola virus cells can stop the virus from infecting, providing new understanding of how the virus suppresses the human immune system
Disabling a protein in Ebola virus cells can stop the virus from replicating and infecting the host, according to researchers from the Icahn School of Medicine at Mount Sinai. The data are published in July in the journal Cell Host and Microbe.
Ebola viruses cause severe disease in humans because they can deactivate the innate immune system. Christopher Basler, PhD, Associate Professor of Microbiology at Mount Sinai and his team have studied how Ebola viruses evade the immune system, and discovered that a viral protein called VP35 is critical to deactivating the immune system. They found that when VP35 interacts with an important cellular protein called PACT, it blocks PACT from activating the immune system, allowing the virus to spread.
“Ebola viruses are extremely lethal, and are a great threat to human health as a bioweapon,” said Dr. Basler. “Currently, there is no approved vaccine or treatment. Our findings will hopefully pave the way for future antiviral treatments.”
With the help of collaborators at the University of Texas with access to special high containment facilities, Dr. Basler and his team infected healthy cells with Ebola virus cells that had mutated versions of VP35. The mutations disabled VP35’s ability to interact with PACT, therefore allowing it to activate the immune system and prevent the virus from replicating. Next, the researchers overexpressed PACT in healthy cells, and infected them with Ebola virus cells. They found that overexpressing PACT also inhibited viral replication.
Armed with this discovery, Dr. Basler and his team hope to develop drugs that disrupt the interaction of VP35 with PACT, or drugs that overexpress PACT.
The work was supported in part by National Institutes of Health grants AI059536 and AI093786 .
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
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About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, 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.