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Active HIV in large white blood cells may drive cognitive impairment in infected mice

June 07, 2018

Corresponding Author: David J. Volsky, PhD, Professor of Medicine and Pathology, Icahn School of Medicine at Mount Sinai; Mary Jane Potash PhD, Associate Professor of Medicine and Pathology, Icahn School of Medicine at Mount Sinai.

Bottom Line: An experimental model of HIV infection in mice, developed by Mount Sinai researchers, has shown that HIV causes learning and memory dysfunction, a cognitive disease that is now observed in about half of HIV infected people that worsens with age, and is currently incurable.

Results: Researchers genetically engineered a rodent version of HIV known as EcoHIV that reproduces many features of human infection. Once infected, mice carry EcoHIV for their lifetimes and the virus remains transmissible. Of particular clinical relevance, within a month of infection all mice failed in tests of learning and memory, like in people on antiretroviral therapy. These problems could not be reversed using standard antiretroviral drugs.

Why the Research Is Interesting: This is the first small animal model that reproduces the establishment of viral reservoirs and mild brain disease observed in HIV infected people.

When: The study examined data from 2012-2017

What: The study measured EcoHIV levels, anti-EcoHIV immune responses, EcoHIV infectivity and capacity to learn of infected mice.

How: Mice were infected by EcoHIV, and virus levels were measured by extremely sensitive amplification of DNA and RNA, efficient protein detection directly and by fluorescence microscopy. The ability to learn was measured by training mice to first recognize and then remember visual symbols swimming toward them.

Study Conclusions: EcoHIV infection of mice can be used to develop and test new drugs against HIV, including targeting reservoirs of infectious virus, as well as drugs directed specifically to restore normal brain function damaged by HIV infection, despite antiretroviral therapy.

Paper Title: EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of cognitive impairment.

Said Mount Sinai's Dr. Volsky of the research: "Cognitive impairment is a common problem in a wide variety of human conditions including diabetes, aging, and Alzheimer's disease. Studies in the EcoHIV model of cognitive impairment may have broad implications for better understanding and treatment of these conditions in other disease states."
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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 seven 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 System includes approximately 7,100 primary and specialty care physicians; 10 joint-venture ambulatory surgery centers; more than 140 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. 13 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, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in four other specialties in the 2017-2018 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked in six out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and 50th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally. For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.

The Mount Sinai Hospital / Mount Sinai School of Medicine

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