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

A Bosque, V Planelles - Blood, The Journal of the American …, 2009 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2009ashpublications.org
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 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 …
Abstract
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 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-κB, 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 κB/NFAT transcription factor binding sites.
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