Submitted July 15, 2008
Accepted September 17, 2008
Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells
Alberto Bosque and Vicente Planelles*
Department of Pathology, University of Utah, Salt Lake City, UT, United States
* Corresponding author; email: vicente.planelles{at}path.utah.edu.
The use of antiretroviral therapy in human immunodeficiency virus type 1 (HIV-1) infected patients does not lead to virus eradication. This is due, to a significant degree, to the fact that HIV-1 can establish a highly stable reservoir of latently infected cells. In this work, we describe an ex vivo experimental system that generates high levels of HIV-1 latently infected memory cells using primary CD4+ T cells. Using this model, we were able to dissect the T cell-signaling pathways and to characterize the long terminal repeat (LTR) cis-acting elements involved in reactivation of HIV-1 in memory CD4+ T cells. We conclude that Lck and NFAT, but not NF-
B, are required for optimal latent virus reactivation in memory T cells. We also find that the cis-acting elements which are critical toward HIV-1 reactivation are the Sp1 and B/NFAT transcription factor binding sites.
