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 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-kappaB, 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 kappaB/NFAT transcription factor binding sites.
Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
Alberto
A
Bosque
Vicente
V
Planelles
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D005816:Genetic Complementation Test; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007668:Kidney / Q000166:cytology; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D020079:Terminal Repeat Sequences / Q000235:genetics; D017735:Virus Latency / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016329:Sp1 Transcription Factor