HIV: Loyola Study Suggests a Way to Stop Virus | Loyola Medicine
Thursday, December 7, 2017

Loyola Study Suggests a Way to Stop HIV in its Tracks

MAYWOOD, IL – When HIV-1 infects an immune cell, the virus travels to the nucleus so quickly there's not enough time to set off the cell's alarm system.
 
Now, a Loyola University Chicago study has discovered the protein that helps the virus travel so fast. Researchers found that without this protein, the virus became stranded in the cytoplasm, where it was detected by the viral defense system. (The cytoplasm is the portion of the cell outside the nucleus.)
 
"By preventing its normal movement, we essentially turned HIV-1 into a sitting duck for cellular sensors,” said Edward M. Campbell, PhD, corresponding author of the study, published in the Proceedings of the National Academy of Sciences. Campbell is an associate professor in the Department of Microbiology and Immunology of Loyola University Chicago Stritch School of Medicine.
 
HIV-1 infects and kills immune system cells, including T cells and macrophages that were used in the study. This cripples the immune system, making the patient vulnerable to common bacteria, viruses and other pathogens that are usually harmless in people with healthy immune systems.
 
After HIV-1 enters a cell, it has to work its way through the cytoplasm to the nucleus. Once inside the nucleus, HIV-1 takes control of the cell and makes additional HIV-1 copies. But getting through the cytoplasm is not easy. Cytoplasm consists of fluid that is thick with proteins and structures such as mitochondria. “Something the size of a virus cannot just diffuse through the cytoplasm," Campbell said. "It would be like trying to float to the bathroom in a very crowded bar. You need to have a plan.”  
 
HIV-1 is able to get to the nucleus quickly via tubular tracks called microtubules. The virus attaches itself to a molecular motor called dynein, which moves down the microtubule like a train car on tracks.
 
Campbell and colleagues discovered the "ticket" HIV-1 needs to get on the train -- a protein called bicaudal D2. HIV-1 binds to bicaudal D2, which then recruits the dynein molecular motor to transport the HIV-1 towards the nucleus.
 
The finding raises the possibility of developing a drug that would prevent HIV-1 from binding to bicaudal D2, thus stranding the virus in the cytoplasm. This would not only prevent infection, but also give the cell time to turn on antiviral genes that would protect it and neighboring cells from infection.
 
The study is titled "Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection."
 
In addition to Campbell, other co-authors are Adarsh Dharan, PhD, (first author), Omar Abdel-Rahim, Sevnur Komurlu Keceli, PhD,  and Sabrina Imam of Loyola and Silvana Opp, PhD, and Felipe Diaz-Griffero, PhD, of Albert Einstein College of Medicine.

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Loyola Medicine is a quaternary care system based in the western suburbs of Chicago that includes Loyola University Medical Center (LUMC) in Maywood, Gottlieb Memorial Hospital (GMH) in Melrose Park, MacNeal Hospital in Berwyn and convenient locations offering primary and specialty care services from more than 1,772 physicians throughout Cook, Will and DuPage counties. LUMC is a 547-licensed-bed hospital that includes the William G. and Mary A. Ryan Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, a Level 1 trauma center, Illinois's largest burn center, a certified comprehensive stroke center and a children’s hospital. The medical center campus is also home to Loyola University Chicago Stritch School of Medicine, Loyola University Chicago Marcella Niehoff School of Nursing and the Loyola Center for Fitness. GMH is a 247-licensed-bed community hospital with 150 physician offices, an adult day care program, the Gottlieb Center for Fitness, the Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park. MacNeal Hospital is a 374-bed teaching hospital with advanced inpatient and outpatient medical, surgical and psychiatric services, advanced diagnostics and treatments in a convenient community setting. Loyola Medicine is a member of Trinity Health, one of the nation’s largest health systems with 94 hospitals in 22 states.

About Trinity Health

Trinity Health is one of the largest multi-institutional Catholic health care delivery systems in the nation, serving diverse communities that include more than 30 million people across 22 states. Trinity Health includes 93 hospitals, as well as 122 continuing care programs that include PACE, senior living facilities, and home care and hospice services. Its continuing care programs provide nearly 2.5 million visits annually. Based in Livonia, Mich., and with annual operating revenues of $17.6 billion and assets of $23.4 billion, the organization returns $1.1 billion to its communities annually in the form of charity care and other community benefit programs. Trinity Health employs about 131,000 colleagues, including 7,500 employed physicians and clinicians. Committed to those who are poor and underserved in its communities, Trinity Health is known for its focus on the country's aging population. As a single, unified ministry, the organization is the innovator of Senior Emergency Departments, the largest not-for-profit provider of home health care services — ranked by number of visits — in the nation, as well as the nation’s leading provider of PACE (Program of All Inclusive Care for the Elderly) based on the number of available programs. For more information, visit www.trinity-health.org. You can also follow @TrinityHealthMI on Twitter.