PROJECT
Transmission of Immunodeficiency Viruses

The human immunodeficiency virus (HIV) is predominantly transmitted across the body surfaces of the genital, rectal, and oral cavities. Cells within these tissues likely contribute to virus capture and the initiation of infection. A particular type of white blood cell, the dendritic cell, is one of the first white blood cells to encounter the virus. The normal function of dendritic cells in the immune system is to capture pathogens and present them to the immune system to activate protective immunity, however, this does not occur successfully in the face of HIV, and, in fact, HIV exploits the dendritic cell system.

Dendritic cells easily capture HIV (entrapping it and becoming infected by it) and can rapidly spread infection to the more susceptible CD4 T cells, readily amplifying virus spread. Moreover, HIV can modify the functions of dendritic cells to favor virus spread over immune activation to clear infection.

The biology of dendritic cell–virus interactions is being studied to improve our understanding of these events. Council researchers are exploring how interactions with other cell types (T cells and epithelial cells) influence this biology and how HIV subverts normal dendritic cell-driven immunity to promote infection. Novel strategies are being tested for their ability to activate mucosal dendritic cells in vitro and in vivo in order to suppress virus growth while boosting immunity. Because herpes simplex virus (HSV) increases HIV transmission researchers are also studying whether HSV-induced changes in dendritic cell function facilitate enhanced HIV spread across the mucosa. This research will help advance strategies to prevent HIV transmission through vaccines and microbicides.

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Population Council researchers

Current: Melissa Robbiani, Loreley Villamide-Herrera, Ines Frank, Jessica Kenney, Onome Akpogheneta, Federica Crostarosa, Nina Derby, Edith Jasny, Panagiotis Vagenas, Meropi Aravantinou, Rachel Singer, Vennansha Williams

Former: Gavin Morrow, Silvia Peretti, Natalia Teleshova, Susanna Trapp, Stuart Turville, Laurence Vachot, Seol-Young Han, Jennifer Jones, Todd Miller, John Santos, Andrew Shaw

Non-Council collaborators

Jim Blanchard (Tulane National Primate Research Center, Covington, Louisiana)

Agegnehu Gettie (Aaron Diamond AIDS Research Center, New York, New York)

Jeffrey Lifson (SAIC/National Cancer Institute, Frederick, Maryland)

Nikolaus Romani (University of Innsbruck, Austria)

Alexandra Trkola (University Hospital Zurich, Switzerland)

Andres Salazar (Oncovir, Washington, DC)

Donors

US National Institutes of Health

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