NEW RESEARCH BY VGTI FLORIDA SCIENCE DIRECTOR DEMONSTRATES HOW HIV DISABLES THE IMMUNE SYSTEM

Research helps focus future studies to specifically target the series of cellular interactions that cause the body to drop its guard

March 8, 2010

PORT ST. LUCIE, Fla. -- New research conducted by the scientific director for VGTI Florida and his colleagues at the University of Montreal, in collaboration with scientists from the NIH and the McGill University Hospital center, may soon lead to an expansion of the drug arsenal used to fight HIV. The research sheds new light on how HIV gradually weakens the body's immune system and highlights the need for new research into therapies that will target the chain of events that cause the progression of the disease.

The study, published in the March 7 online edition of the journal Nature Medicine, describes the pivotal role of two molecules, PD-1 and IL-10, in impairing the function of disease-fighting T-cells known as CD4 T-cells - a phenomenon that weakens the body's immune system.

Specifically, the researchers found that when HIV invades the body, bacterial products are released from the gut and white blood cells respond by releasing a protein on the surface of the cell called PD-1. Heightened levels of PD-1 lead to the activation of a gene that produces another protein called IL-10. Both of these proteins (PD-1 and IL-10) are known to appear at increased levels during HIV infection.

"We are the first to show that these two molecules work together to shut down the function of CD4 T-cells in HIV patients. This in turn, may lead to paralysis of the immune system and an accelerated disease progression," said Dr. Rafick-Pierre Sékaly, scientific director of VGTI Florida, a professor at the University of Montreal and researcher at the Research Center of the University of Montreal Hospital Center.

"Our results suggest that it is important to block both IL-10 and PD-1 interactions to restore the immune response during HIV infection," said Dr. Sékaly. "We believe that immunotherapies that target PD-1 and IL-10 should be part of the arsenal used to restore immune function in HIV-infected subjects."

About HIV treatment:

During the last 20 years, treatment of HIV/AIDS has evolved and now uses highly active anti-retroviral therapy (HAART) that involves at least three active anti-retroviral medications. The HAART "cocktail" is a potent suppressor of viral replication in the blood. Although, HAART has been shown to delay the progression of AIDS and prolong life, it is not curative. The quest for improved treatments continues.

About the study:

The article "PD-1 Induced IL-10 Production by Monocytes Impairs CD4 T-Cell Activation during HIV Infection," published in Nature, was authored by Elias A. Said, Franck P. Dupuy, Lydie Trautmann, Yuwei Zhang, Yu Shi, Mohamed El-Far, Brenna J. Hill, Alessandra Noto, Petronela Ancuta, Yoav Peretz, Simone G. Fonseca, Julien Van Grevenynghe, Mohamed R. Boulassel, Julie Bruneau, Naglaa H. Shoukry, Jean-Pierre Routy, Daniel  C. Douek, Elias K. Haddad, Rafick P. Sekaly.

About VGTI Florida:

VGTI Florida is the Florida-funded expansion of Oregon Health & Science University's highly successful Vaccine and Gene Therapy Institute. The institute was created through a $60 million investment by the state of Florida in January 2008 and $53 million in matching funds provided by the city of Port St. Lucie. Research at the facility will focus on vaccine development with a special focus on vaccines and therapeutics that protect the aging population, which is the most vulnerable to disease.