Elite controllers constitute a rare group of HIV-infected individuals who control HIV replication and maintain normal CD4 cell counts without antiretroviral therapy (ART). The mechanisms involved in the control of infection are poorly understood. This review will focus on the identification of signaling pathways upregulated or downregulated in different memory T-cell subsets in elite controllers by using systems biology approaches. Features of memory T cells in simian immunodeficiency virus (SIV) natural hosts will be also highlighted. Finally, we will discuss how these approaches will guide the development of new vaccines and therapeutic interventions.
Studies by our group identified the FOXO3a, STAT5, and Wnt/beta-catenin pathways as unique molecular signatures associated with survival of memory T cells in elite controllers. These discoveries open the path for the design of new strategies to prevent T-cell depletion in HIV-infected individuals.
The use of systems biology to identify molecular pathways involved in the survival of memory T cells is a powerful tool toward the understanding of mechanisms of HIV control in elite controllers. This will help to identify correlates of immune protection leading to the design of effective HIV vaccines and new targeted therapeutic interventions.
aVaccine and Gene Therapy Institute-Florida (VGTI-FL), Port Sainte-Lucie, Florida, USA
bCentre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM), Saint-Luc Hospital, Canada
cDepartement of Microbiology and Immunology, Université de Montréal, Montréal, Québec, Canada
Correspondance to Rafick-Pierre Sékaly, VGTI-FL, 11350 SW Village Parkway, Port Sainte-Lucie, FL 34987, USA Tel: +1 7723454780; fax: +1 772 345 3675; e-mail: firstname.lastname@example.org
Supported by funds from the US National Institutes of Health (IDPIDA028871-01, AI076174-01A1) and the Bill and Melinda Gates Foundation (SEKALY06VIMC0, GH-HTR-05-02).