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Blood, 1 January 2009, Vol. 113, No. 1, pp. 58-65.
Prepublished online as a Blood First Edition Paper on October 10, 2008; DOI 10.1182/blood-2008-07-168393.


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IMMUNOBIOLOGY

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

Alberto Bosque1, and Vicente Planelles1

1 Department of Pathology, University of Utah, Salt Lake City

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-{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.


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