New findings from a Université de Montréal and the Vaccine and Gene Therapy Institute of Florida (VGTI) study, in collaboration with scientists from the NIH and the McGill University Health Center, may soon lead to an expansion of the drug arsenal used to fight HIV. The Canada-U.S. study published today in the journal Nature Medicine characterizes the pivotal role of two molecules, PD-1 and IL-10, in influencing the function of CD4/T-helper cells and altering their ability to fight HIV.
"Our findings show that the membrane protein PD-1 is up-regulated during HIV infection by the release of bacterial products from the gut and this subsequently increases the production of a cell derived factor, IL-10 that paralyses the immune system ," says senior author Dr. Rafick-Pierre Sékaly, a professor at the Université de Montréal, researcher at the Centre de Recherche du CHUM and scientific director of the Vaccine and Gene Therapy Institute of Florida. "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 ."
"Our results suggest that it is important to block both IL-10 and PD-1 interactions to restore the immune response during HIV infection," says 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.
Partners in research:
This study was funded by the Canadian Institutes of Health Research, the Canadian Foundation for Infectious Diseases, the Fonds de la recherche en santé du Québec, the National Institutes of Health, the Canadian Foundation for AIDS Research and the Canadian Network for Vaccines and Immunotherapeutics.
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.
On the Web:
About Nature Medicine: www.nature.com/nm
About the Université de Montréal: www.umontreal.ca/english
About the Centre de Recherche du CHUM: www.crchum.qc.ca
About the Vaccine and Gene Therapy Institute of Florida: www.ohsu.edu/vgti
Journal
Nature Medicine