Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells

The use of antiretroviral therapy in HIV 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 Introduction 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 nuclear factor of activated T cells (NFAT), but not NF-kappa B, are required for optimal latent virus reactivation in memory T cells. We also found that the cis-acting elements which are critical toward HIV-1 reactivation are the Sp1 and kappa B/NFAT transcription factor binding sites. (Blood. 2009; 113: 58-65)