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

Blood - Tập 113 - Trang 58-65 - 2009
Alberto Bosque1, Vicente Planelles1
1Department of Pathology, University of Utah, Salt Lake City

Tóm tắt

AbstractThe 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.

Tài liệu tham khảo

Finzi, 1997, Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy., Science, 278, 1295, 10.1126/science.278.5341.1295 Chun, 1997, Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection., Nature, 387, 183, 10.1038/387183a0 Folks, 1989, Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone., Proc Natl Acad Sci U S A, 86, 2365, 10.1073/pnas.86.7.2365 Antoni, 1994, NF-kappa B-dependent and -independent pathways of HIV activation in a chronically infected T cell line., Virology, 202, 684, 10.1006/viro.1994.1390 Jordan, 2003, HIV reproducibly establishes a latent infection after acute infection of T cells in vitro., Embo J, 22, 1868, 10.1093/emboj/cdg188 Folks, 1987, Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line., Science, 238, 800, 10.1126/science.3313729 Brooks, 2001, Generation of HIV latency during thymopoiesis., Nat Med, 7, 459, 10.1038/86531 Lahm, 1985, Characterization of recombinant human interleukin-2 with micromethods., J Chromatogr, 326, 357, 10.1016/S0021-9673(01)87461-6 Svarovskaia, 2004, Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions., J Virol, 78, 3210, 10.1128/JVI.78.7.3210-3222.2004 Simm, 1995, Aberrant Gag protein composition of a human immunodeficiency virus type 1 vif mutant produced in primary lymphocytes., J Virol, 69, 4582, 10.1128/JVI.69.7.4582-4586.1995 Messi, 2003, Memory and flexibility of cytokine gene expression as separable properties of human T(H)1 and T(H)2 lymphocytes., Nat Immunol, 4, 78, 10.1038/ni872 Zhu, 2001, Comparison of cell cycle arrest, transactivation, and apoptosis induced by the simian immunodeficiency virus SIVagm and human immunodeficiency virus type 1 vpr genes., J Virol, 75, 3791, 10.1128/JVI.75.8.3791-3801.2001 Gomez-Benito, 2005, Apo2L/TRAIL is an indirect mediator of apoptosis induced by interferon-alpha in human myeloma cells., FEBS Lett, 579, 6217, 10.1016/j.febslet.2005.10.007 Vandegraaff, 2001, Specific inhibition of human immunodeficiency virus type 1 (HIV-1) integration in cell culture: putative inhibitors of HIV-1 integrase., Antimicrob Agents Chemother, 45, 2510, 10.1128/AAC.45.9.2510-2516.2001 Butler, 2001, A quantitative assay for HIV DNA integration in vivo., Nat Med, 7, 631, 10.1038/87979 Dehart, 2005, The ataxia telangiectasia-mutated and Rad3-related protein is dispensable for retroviral integration., J Virol, 79, 1389, 10.1128/JVI.79.3.1389-1396.2005 Rivino, 2004, Chemokine receptor expression identifies Pre-T helper (Th)1, Pre-Th2, and nonpolarized cells among human CD4+ central memory T cells., J Exp Med, 200, 725, 10.1084/jem.20040774 Andersen, 2006, HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT., PLoS Pathog, 2, e127, 10.1371/journal.ppat.0020127 Challita-Eid, 1998, Inhibition of HIV type 1 infection with a RANTES-IgG3 fusion protein., AIDS Res Hum Retroviruses, 14, 1617, 10.1089/aid.1998.14.1617 Brenchley, 2004, T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis., J Virol, 78, 1160, 10.1128/JVI.78.3.1160-1168.2004 Kane, 2000, Signal transduction by the TCR for antigen., Curr Opin Immunol, 12, 242, 10.1016/S0952-7915(00)00083-2 Isakov, 1987, T-lymphocyte activation: the role of protein kinase C and the bifurcating inositol phospholipid signal transduction pathway., Immunol Rev, 95, 89, 10.1111/j.1600-065X.1987.tb00501.x Bauer, 2000, T cell expressed PKCtheta demonstrates cell-type selective function., Eur J Immunol, 30, 3645, 10.1002/1521-4141(200012)30:12<3645::AID-IMMU3645>3.0.CO;2-# Swaroop, 2001, Inhibition of nuclear transcription factor-kappaB by specific IkappaB kinase peptide inhibitor., Pharm Res, 18, 1631, 10.1023/A:1013051019098 Lin, 2001, T cell receptor signalling., J Cell Sci, 114, 243, 10.1242/jcs.114.2.243 Franke, 1995, The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase., Cell, 81, 727, 10.1016/0092-8674(95)90534-0 Nordheim, 1994, Transcription factors. CREB takes CBP to tango., Nature, 370, 177, 10.1038/370177a0 Osborn, 1989, Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B., Proc Natl Acad Sci U S A, 86, 2336, 10.1073/pnas.86.7.2336 Duh, 1989, Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat., Proc Natl Acad Sci U S A, 86, 5974, 10.1073/pnas.86.15.5974 Ylisastigui, 2004, Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression., Aids, 18, 1101, 10.1097/00002030-200405210-00003 Simon, 1994, Valproic acid reduces the intracellular level of glutathione and stimulates human immunodeficiency virus., Chem Biol Interact, 91, 111, 10.1016/0009-2797(94)90031-0 Lehrman, 2005, Depletion of latent HIV-1 infection in vivo: a proof-of-concept study., Lancet, 366, 549, 10.1016/S0140-6736(05)67098-5 Tesmer, 1993, NF-IL6-mediated transcriptional activation of the long terminal repeat of the human immunodeficiency virus type 1., Proc Natl Acad Sci U S A, 90, 7298, 10.1073/pnas.90.15.7298 Sheridan, 1995, Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro., Genes Dev, 9, 2090, 10.1101/gad.9.17.2090 Ruocco, 1996, Regulation of HIV-1 long terminal repeats by interaction of C/EBP(NF-IL6) and NF-kappaB/Rel transcription factors., J Biol Chem, 271, 22479, 10.1074/jbc.271.37.22479 Perkins, 1994, Transcription factor AP-2 regulates human immunodeficiency virus type 1 gene expression., J Virol, 68, 6820, 10.1128/JVI.68.10.6820-6823.1994 Jones, 1986, Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1., Science, 232, 755, 10.1126/science.3008338 d'Adda di Fagagna, 1995, Molecular and functional interactions of transcription factor USF with the long terminal repeat of human immunodeficiency virus type 1., J Virol, 69, 2765, 10.1128/JVI.69.5.2765-2775.1995 Bohnlein, 1988, The same inducible nuclear proteins regulates mitogen activation of both the interleukin-2 receptor-alpha gene and type 1 HIV., Cell, 53, 827, 10.1016/0092-8674(88)90099-2 Douek, 2003, T cell dynamics in HIV-1 infection., Annu Rev Immunol, 21, 265, 10.1146/annurev.immunol.21.120601.141053 Persaud, 2003, Latency in human immunodeficiency virus type 1 infection: no easy answers., J Virol, 77, 1659, 10.1128/JVI.77.3.1659-1665.2003 Kim, 2006, Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency., Embo J, 25, 3596, 10.1038/sj.emboj.7601248 Chen, 1994, Distinct modes of human immunodeficiency virus type 1 proviral latency revealed by superinfection of nonproductively infected cell lines with recombinant luciferase-encoding viruses., J Virol, 68, 654, 10.1128/JVI.68.2.654-660.1994 Cannon, 1994, Analysis of Tat function in human immunodeficiency virus type 1-infected low-level-expression cell lines U1 and ACH-2., J Virol, 68, 1993, 10.1128/JVI.68.3.1993-1997.1994 Butera, 1994, Human immunodeficiency virus type 1 RNA expression by four chronically infected cell lines indicates multiple mechanisms of latency., J Virol, 68, 2726, 10.1128/JVI.68.4.2726-2730.1994 Vicart, 2006, Increased chromatin association of Sp1 in interphase cells by PP2A-mediated dephosphorylations., J Mol Biol, 364, 897, 10.1016/j.jmb.2006.09.036 Lacroix, 2002, Sp1 transcriptional activity is up-regulated by phosphatase 2A in dividing T lymphocytes., J Biol Chem, 277, 9598, 10.1074/jbc.M111444200 Giffin, 2003, Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element., Nat Struct Biol, 10, 800, 10.1038/nsb981 Dienz, 2007, Accumulation of NFAT mediates IL-2 expression in memory, but not naive, CD4+ T cells., Proc Natl Acad Sci U S A, 104, 7175, 10.1073/pnas.0610442104 Round, 2007, Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors., Nat Immunol, 8, 154, 10.1038/ni1422 Brooks, 2003, Molecular characterization, reactivation, and depletion of latent HIV., Immunity, 19, 413, 10.1016/S1074-7613(03)00236-X Abraham, 2004, Jurkat T cells and development of the T-cell receptor signalling paradigm., Nat Rev Immunol, 4, 301, 10.1038/nri1330