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Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat is a multifunctional protein that contributes to several pathological symptoms of HIV-1 infection as well as playing a critical role in virus replication. Tat is a robust transactivating protein that induces a variety of effects by altering the expression levels of cellular and viral genes. The functions of Tat are therefore primarily related to its role in modulation of gene expression. In this review the functions of HIV-1 Tat that have been well documented, as well as a number of novel functions that have been proposed for this protein, are discussed. Since some of the functions of Tat vary in different cell types in a concentration-dependent manner and because Tat sometimes exerts the same activity through different pathways, study of this protein has at times yielded conflicting and controversial results. Due to its pivotal role in viral replication and in disease pathogenesis, Tat and the cellular pathways targeted by Tat are potential targets for new anti-HIV drugs.

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2010-01-01
2024-03-28
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References

  1. Ambrosino, C., Ruocco, M. R., Chen, X., Mallardo, M., Baudi, F., Trematerra, S., Quinto, I., Venuta, S. & Scala, G.(1997). HIV-1 Tat induces the expression of the interleukin-6 (IL6) gene by binding to the IL6 leader RNA and by interacting with CAAT enhancer-binding protein β (NF-IL6) transcription factors. J Biol Chem 272, 14883–14892.[CrossRef] [Google Scholar]
  2. Ammosova, T., Berro, R., Jerebtsova, M., Jackson, A., Charles, S., Klase, Z., Southerland, W., Gordeuk, V. R., Kashanchi, F. & Nekhai, S.(2006). Phosphorylation of HIV-1 Tat by CDK2 in HIV-1 transcription. Retrovirology 3, 78[CrossRef] [Google Scholar]
  3. Aoki, Y. & Tosato, G.(2004). HIV-1 Tat enhances Kaposi sarcoma-associated herpesvirus (KSHV) infectivity. Blood 104, 810–814.[CrossRef] [Google Scholar]
  4. Barton, C. H., Biggs, T. E., Mee, T. R. & Mann, D. A.(1996). The human immunodeficiency virus type 1 regulatory protein Tat inhibits interferon-induced iNos activity in a murine macrophage cell line. J Gen Virol 77, 1643–1647.[CrossRef] [Google Scholar]
  5. Bennasser, Y. & Bahraoui, E.(2002). HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: involvement of protein kinase C-βII and -δ. FASEB J 16, 546–554.[CrossRef] [Google Scholar]
  6. Bennasser, Y., Yeung, M. L. & Jeang, K.-T.(2006). HIV-1 TAR RNA subverts RNA interference in transfected cells through sequestration of TAR RNA-binding protein, TRBP. J Biol Chem 281, 27674–27678.[CrossRef] [Google Scholar]
  7. Bernard-Gallon, D., Bosviel, R., Delort, L., Fontana, L., Chamoux, A., Rabiau, N., Kwiatkowski, F., Chalabi, N., Satih, S. & Bignon, Y. J.(2008). DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk. Mol Cancer 7, 36[CrossRef] [Google Scholar]
  8. Bowater, R. P., Borts, R. H. & White, M. F.(2009). DNA damage: from causes to cures. Biochem Soc Trans 37, 479–481.[CrossRef] [Google Scholar]
  9. Bres, V., Kiernan, R., Emiliani, S. & Benkirane, M.(2002). Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication. J Biol Chem 277, 22215–22221.[CrossRef] [Google Scholar]
  10. Campbell, G. R., Pasquier, E., Watkins, J., Bourgarel-Rey, V., Peyrot, V., Esquieu, D., Barbier, P., de-Mareuil, J., Braguer, D. & other authors(2004). The glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosis. J Biol Chem 279, 48197–48204.[CrossRef] [Google Scholar]
  11. Cantaluppi, V., Biancone, L., Boccellino, M., Doublier, S., Benelli, R., Carlone, S., Albini, A. & Camussi, G.(2001). HIV type 1 Tat protein is a survival factor for Kaposi's sarcoma and endothelial cells. AIDS Res Hum Retroviruses 17, 965–976.[CrossRef] [Google Scholar]
  12. Chang, P. Y., Stellrecht, K., Melana, S. & Pogo, B. G. T.(1994). Elements in the long terminal repeat of HIV-1 that interact with nuclear extracts from Jurkat cells persistently infected with vaccinia virus. Virus Res 34, 127–138.[CrossRef] [Google Scholar]
  13. Chauhan, A., Turchan, J., Pocernich, C., Bruce-Keller, A., Roth, S., Butterfield, D. A., Major, E. O. & Nath, A.(2003). Intracellular human immunodeficiency virus Tat expression in astrocytes promotes astrocyte survival but induces potent neurotoxicity at distant sites via axonal transport. J Biol Chem 278, 13512–13519.[CrossRef] [Google Scholar]
  14. Chen, S., Chen, R., He, M., Pang, R., Tan, Z. & Yang, M.(2009). Design, synthesis, and biological evaluation of novel quinoline derivatives as HIV-1 Tat–TAR interaction inhibitors. Bioorg Med Chem 17, 1948–1956.[CrossRef] [Google Scholar]
  15. Cheng, J., Nath, A., Knudsen, B., Hochman, S., Geiger, J. D., Ma, M. & Magnuson, D. S.(1998). Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein. Neuroscience 82, 97–106. [Google Scholar]
  16. D'Orso, I. & Frankel, A. D.(2009). Tat acetylation modulates assembly of a viral-host RNA–protein transcription complex. Proc Natl Acad Sci U S A 106, 3101–3106.[CrossRef] [Google Scholar]
  17. da Silva, F. H., Dalberto, T. P. & Nardi, N. B.(2006). Beyond retrovirus infection: HIV meets gene therapy. Genet Mol Biol 29, 367–379.[CrossRef] [Google Scholar]
  18. Dabrowska, A., Kim, N. & Aldovini, A.(2008). Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes. J Immunol 181, 8460–8477.[CrossRef] [Google Scholar]
  19. Daelemans, D., Schols, D., Witvrouw, M., Pannecouque, C., Hatse, S., van-Dooren, S., Hamy, F., Klimkait, T., de-Clercq, E. & VanDamme, A. M.(2000). A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry. Mol Pharmacol 57, 116–124. [Google Scholar]
  20. Dalakas, M. C.(2006). Therapeutic targets in patients with inflammatory myopathies: present approaches and a look to the future. Neuromuscul Disord 16, 223–236.[CrossRef] [Google Scholar]
  21. de Mareuil, J., Carre, M., Barbier, P., Campbell, G. R., Lancelot, S., Opi, S., Esquieu, D., Watkins, J. D., Prevot, C. & other authors(2005). HIV-1 Tat protein enhances microtubule polymerization. Retrovirology 2, 5[CrossRef] [Google Scholar]
  22. Demarchi, F., Gutierrez, M. I. & Giacca, M.(1999). Human immunodeficiency virus type 1 Tat protein activates transcription factor NF-κB through the cellular interferon-inducible, double-stranded RNA-dependent protein kinase, PKR. J Virol 73, 7080–7086. [Google Scholar]
  23. Deng, L., de-la-Fuente, C., Fu, P., Wang, L., Donnelly, R., Wade, J. D., Lambert, P., Li, H., Lee, C. G. & Kashanchi, F.(2000). Acetylation of HIV-1 Tat by CBP/P300 increases transcription of integrated HIV-1 genome and enhances binding to core histones. Virology 277, 278–295.[CrossRef] [Google Scholar]
  24. Deng, L., Wang, D., de-la-Fuente, C., Wang, L., Li, H., Lee, C. G., Donnelly, R., Wade, J. D., Lambert, P. & Kashanchi, F.(2001). Enhancement of the p300 HAT activity by HIV-1 Tat on chromatin DNA. Virology 289, 312–326.[CrossRef] [Google Scholar]
  25. Deregibus, M. C., Cantaluppi, V., Doublier, S., Brizzi, M. F., Deambrosis, I., Albini, A. & Camussi, G.(2002). HIV-1-Tat protein activates phosphatidylinositol 3-kinase/AKT-dependent survival pathways in Kaposi's sarcoma cells. J Biol Chem 277, 25195–25202.[CrossRef] [Google Scholar]
  26. Drewes, G., Ebneth, A. & Mandelkow, E. M.(1998). MAPs, MARKs and microtubule dynamics. Trends Biochem Sci 23, 307–311.[CrossRef] [Google Scholar]
  27. Epie, N., Ammosova, T., Sapir, T., Voloshin, Y., Lane, W. S., Turner, W., Reiner, O. & Nekhai, S.(2005). HIV-1 Tat interacts with LIS1 protein. Retrovirology 2, 6[CrossRef] [Google Scholar]
  28. Evans, P., Dampier, W., Ungar, L. & Tozeren, A.(2009). Prediction of HIV-1 virus-host protein interactions using virus and host sequence motifs. BMC Med Genomics 2, 27[CrossRef] [Google Scholar]
  29. Fanales-Belasio, E., Moretti, S., Fiorelli, V., Tripiciano, A., Cossut, M. R. P., Scoglio, A., Collacchi, B., Nappi, F., Macchia, I. & other authors(2009). HIV-1 Tat addresses dendritic cells to induce a predominant Th1-type adaptive immune response that appears prevalent in the asymptomatic stage of infection. J Immunol 182, 2888–2897.[CrossRef] [Google Scholar]
  30. Ferrari, A., Pellegrini, V., Arcangeli, C., Fittipaldi, A., Giacca, M. & Beltram, F.(2003). Caveolae-mediated internalization of extracellular HIV-1 Tat fusion proteins visualized in real time. Mol Ther 8, 284–294.[CrossRef] [Google Scholar]
  31. Fu, W., Sanders-Beer, B. E., Katz, K. S., Maglott, D. R., Pruitt, K. D. & Ptak, R. G.(2009). Human immunodeficiency virus type 1, human protein interaction database at NCBI. Nucleic Acids Res 37, D417[CrossRef] [Google Scholar]
  32. Futaki, S., Suzuki, T., Ohashi, W., Yagami, T., Tanaka, S., Ueda, K. & Sugiura, Y.(2001). Arginine-rich peptides. An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery. J Biol Chem 276, 5836–5840.[CrossRef] [Google Scholar]
  33. Gallo, R. C.(1999). Tat as one key to HIV-induced immune pathogenesis and Tat toxoid as an important component of a vaccine. Proc Natl Acad Sci U S A 96, 8324–8326.[CrossRef] [Google Scholar]
  34. Gandhi, N., Saiyed, Z., Thangavel, S., Rodriguez, J., Rao, K. V. K. & Nair, M. P. N.(2009). Differential effects of HIV type 1 clade B and clade C Tat protein on expression of proinflammatory and anti-inflammatory cytokines by primary monocytes. AIDS Res Hum Retroviruses 25, 691–699.[CrossRef] [Google Scholar]
  35. Giacca, M.(2005). HIV-1 Tat, apoptosis and the mitochondria: a tubulin link? Retrovirology 2, 7[CrossRef] [Google Scholar]
  36. Giunta, B., Hou, H., Zhu, Y., Rrapo, E., Tian, J., Takashi, M., Commins, D., Singer, E., He, J. & other authors(2009). HIV-1 Tat contributes to Alzheimer's disease-like pathology in PSAPP mice. Int J Clin Exp Pathol 2, 433–443. [Google Scholar]
  37. Gorrill, T., Feliciano, M., Mukerjee, R., Sawaya, B. E., Khalili, K. & White, M. K.(2006). Activation of early gene transcription in polyomavirus BK by human immunodeficiency virus type 1 Tat. J Gen Virol 87, 1557–1566.[CrossRef] [Google Scholar]
  38. Gupta, S., Boppana, R., Mishra, G. C., Saha, B. & Mitra, D.(2008). HIV-1 Tat suppresses gp120-specific T cell response in IL-10-dependent manner. J Immunol 180, 79–88.[CrossRef] [Google Scholar]
  39. Harrich, D., Ulich, C., Garcia-Martinez, L. & Gaynor, R. B.(1997). Tat is required for efficient HIV-1 reverse transcription. EMBO J 16, 1224–1235.[CrossRef] [Google Scholar]
  40. Haughey, N. J. & Mattson, M. P.(2002). Calcium dysregulation and neuronal apoptosis by the HIV-1 proteins Tat and gp120. J Acquir Immune Defic Syndr 31, S55–S61.[CrossRef] [Google Scholar]
  41. Hu, M., Wang, J., Chen, P. & Reilly, R. M.(2006). HIV-1 Tat peptide immunoconjugates differentially sensitize breast cancer cells to selected antiproliferative agents that induce the cyclin-dependent kinase inhibitor p21WAF-1/CIP-1. Bioconjug Chem 17, 1280–1287.[CrossRef] [Google Scholar]
  42. Hwang, S., Tamilarasu, N., Kibler, K., Cao, H., Ali, A., Ping, Y. H., Jeang, K. T. & Rana, T. M.(2003). Discovery of a small molecule Tat-trans-activation-responsive RNA antagonist that potently inhibits human immunodeficiency virus-1 replication. J Biol Chem 278, 39092–39103.[CrossRef] [Google Scholar]
  43. Inoue, Y., Asanuma, T., Smith, N., Saunders, D., Oblander, J., Kotake, Y., Floyd, R. A. & Towner, R. A.(2007). Modulation of Fas-FasL related apoptosis by PBN in the early phases of choline deficient diet-mediated hepatocarcinogenesis in rats. Free Radic Res 41, 972–980.[CrossRef] [Google Scholar]
  44. Ju, S. M., Song, H. Y., Lee, J. A., Lee, S. J., Choi, S. Y. & Park, J.(2009). Extracellular HIV-1 Tat up-regulates expression of matrix metalloproteinase-9 via a MAPK-NF-κB dependent pathway in human astrocytes. Exp Mol Med 41, 86–93.[CrossRef] [Google Scholar]
  45. Kameoka, M., Morgan, M., Binette, M., Russell, R. S., Rong, L., Guo, X., Mouland, A., Kleiman, L., Liang, C. & Wainberg, M. A.(2002). The Tat protein of human immunodeficiency virus type 1 (HIV-1) can promote placement of tRNA primer onto viral RNA and suppress later DNA polymerization in HIV-1 reverse transcription. J Virol 76, 3637–3645.[CrossRef] [Google Scholar]
  46. Kim, T. A., Avraham, H. K., Koh, Y. H., Jiang, S., Park, I. W. & Avraham, S.(2003). HIV-1 Tat-mediated apoptosis in human brain microvascular endothelial cells. J Immunol 170, 2629–2637.[CrossRef] [Google Scholar]
  47. Kim, H. J., Martemyanov, K. A. & Thayer, S. A.(2008). Human immunodeficiency virus protein Tat induces synapse loss via a reversible process that is distinct from cell death. J Neurosci 28, 12604–12613.[CrossRef] [Google Scholar]
  48. Klase, Z., Winograd, R., Davis, J., Carpio, L., Hildreth, R., Heydarian, M., Fu, S., McCaffrey, T., Meiri, E. & other authors(2009). HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression. Retrovirology 6, 18[CrossRef] [Google Scholar]
  49. Li, J. C. B., Lee, D. C. W., Cheung, B. K. W. & Lau, A. S. Y.(2005). Mechanisms for HIV Tat upregulation of IL-10 and other cytokine expression: kinase signaling and PKR-mediated immune response. FEBS Lett 579, 3055–3062.[CrossRef] [Google Scholar]
  50. Liang, C. & Wainberg, M. A.(2002). The role of Tat in HIV-1 replication: an activator and/or a suppressor? AIDS Rev 4, 41–49. [Google Scholar]
  51. Licona-Limón, P. & Soldevila, G.(2007). The role of TGF-β superfamily during T cell development: new insights. Immunol Lett 109, 1–12.[CrossRef] [Google Scholar]
  52. Liu, Y., Jones, M., Hingtgen, C. M., Bu, G., Laribee, N., Tanzi, R. E., Moir, R. D., Nath, A. & He, J. J.(2000). Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med 6, 1380–1387.[CrossRef] [Google Scholar]
  53. Mahlknecht, U., Dichamp, I., Varin, A., Lint, C. V. & Herbein, G.(2008). NF-κB-dependent control of HIV-1 transcription by the second coding exon of Tat in T cells. J Leukoc Biol 83, 718–727. [Google Scholar]
  54. Matsui, M., Warburton, R. J., Cogswell, P. C., Baldwin, A. S. & Frelinger, J. A.(1996). Effects of HIV-1 Tat on expression of HLA class I molecules. J Acquir Immune Defic Syndr Hum Retrovirol 11, 233–240.[CrossRef] [Google Scholar]
  55. Mayol, K., Munier, S., Beck, A., Verrier, B. & Guillon, C.(2007). Design and characterization of an HIV-1 Tat mutant: inactivation of viral and cellular functions but not antigenicity. Vaccine 25, 6047–6060.[CrossRef] [Google Scholar]
  56. Melekhovets, Y., Ramezani, A., Kyriakopoulou, L. & Joshi, S.(2001). Tat-RNase H and its use in HIV gene therapy. Gene Ther Mol Biol 6, 69–77. [Google Scholar]
  57. Miller, M. A., Weibel, C., Ferguson, D., Landry, M. L. & Kahn, J. S.(2009). WU polyomavirus in patients infected with HIV or hepatitis C virus, Connecticut, USA, 2007. Emerg Infect Dis [Google Scholar]
  58. Mischiati, C., Pironi, F., Milani, D., Giacca, M., Mirandola, P., Capitani, S. & Zauli, G.(1999). Extracellular HIV-1 Tat protein differentially activates the JNK and ERK/MAPK pathways in CD4 T cells. AIDS 13, 1637–1645.[CrossRef] [Google Scholar]
  59. Miura, Y., Koyanagi, Y. & Mizusawa, H.(2003). TNF-related apoptosis-inducing ligand (TRAIL) induces neuronal apoptosis in HIV-encephalopathy. J Med Dent Sci 50, 17–25. [Google Scholar]
  60. Nakajima, H., Mizuta, N., Fujiwara, I., Sakaguchi, K., Ogata, H., Magae, J., Yagita, H. & Koji, T.(2008). Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver. Apoptosis 13, 1013–1021.[CrossRef] [Google Scholar]
  61. Nekhai, S., Jerebtsova, M., Jackson, A. & Southerland, W.(2007). Regulation of HIV-1 transcription by protein phosphatase 1. Curr HIV Res 5, 3–9. [Google Scholar]
  62. Nunnari, G., Smith, J. A. & Daniel, R.(2008). HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier? J Exp Clin Cancer Res 27, 3[CrossRef] [Google Scholar]
  63. Nyagol, J., Leucci, E., Onnis, A., Falco, G. D., Tigli, C., Sanseverino, F., Torriccelli, M., Palummo, N., Pacenti, L. & other authors(2006). The effects of HIV-1 Tat protein on cell cycle during cervical carcinogenesis. Cancer Biol Ther 5, 684–690.[CrossRef] [Google Scholar]
  64. Ouellet, D. L., Plante, I., Landry, P., Barat, C., Janelle, M. E., Flamand, L., Tremblay, M. J. & Provost, P.(2008). Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res 36, 2353–2365.[CrossRef] [Google Scholar]
  65. Pagans, S., Pedal, A., North, B. J., Kaehlcke, K., Marshall, B. L., Dorr, A., Hetzer-Egger, C., Henklein, P., Frye, R. & other authors(2005). SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biol 3, E41[CrossRef] [Google Scholar]
  66. Paquette, J. C., Guerin, P. J. & Gauthier, E. R.(2005). Rapid induction of the intrinsic apoptotic pathway by L-glutamine starvation. J Cell Physiol 202, 912–921.[CrossRef] [Google Scholar]
  67. Park, I. W., Ullrich, C. K., Schoenberger, E., Ganju, R. K. & Groopman, J. E.(2001). HIV-1 Tat induces microvascular endothelial apoptosis through caspase activation. J Immunol 167, 2766–2771.[CrossRef] [Google Scholar]
  68. Penza, M., Buccigrossi, V., Giannattasio, A., Marco, G. D., Esposito, C., Polito, G., Squeglia, V., Assante, L. R., Ambrosio, R. & Guarino, A.(2008). HIV-1 transactivator factor (Tat) induces damage through a redox mechanism in human intestinal epithelial cells. Dig Liver Dis 40, A97[CrossRef] [Google Scholar]
  69. Perez-Cruz, I., Cárcamo, J. M. & Golde, D. W.(2007). Caspase-8 dependent trail-induced apoptosis in cancer cell lines is inhibited by vitamin C and catalase. Apoptosis 12, 225–234.[CrossRef] [Google Scholar]
  70. Pinney, J. W., Dickerson, J. E., Fu, W., Sanders-Beer, B. E., Ptak, R. G. & Robertson, D. L.(2009). HIV-host interactions: a map of viral perturbation of the host system. AIDS 23, 549–554. [Google Scholar]
  71. Pocernich, C. B., Sultana, R., Mohmmad-Abdul, H., Nath, A. & Butterfield, D. A.(2005). HIV-dementia, Tat-induced oxidative stress, and antioxidant therapeutic considerations. Brain Res Brain Res Rev 50, 14–26.[CrossRef] [Google Scholar]
  72. Poggi, A. & Zocchi, M. R.(2006). HIV-1 Tat triggers TGF-β production and NK cell apoptosis that is prevented by pertussis toxin B. Clin Dev Immunol 13, 369–372.[CrossRef] [Google Scholar]
  73. Price, T. O., Ercal, N., Nakaoke, R. & Banks, W. A.(2005). HIV-1 viral proteins gp120 and Tat induce oxidative stress in brain endothelial cells. Brain Res 1045, 57–63.[CrossRef] [Google Scholar]
  74. Ptak, R. G., Fu, W., Sanders-Beer, B. E., Dickerson, J. E., Pinney, J. W., Robertson, D. L., Rozanov, M. N., Katz, K. S., Maglott, D. R. & Pruitt, K. D.(2008). Cataloguing the HIV type 1 human protein interaction network. AIDS Res Hum Retroviruses 24, 1497–1502.[CrossRef] [Google Scholar]
  75. Pugliese, A., Vidotto, V., Beltramo, T., Petrini, S. & Torre, D.(2005). A review of HIV-1 Tat protein biological effects. Cell Biochem Funct 23, 223–227.[CrossRef] [Google Scholar]
  76. Pumfery, A., Deng, L., Maddukuri, A., de-la-Fuente, C., Li, H., Wade, J. D., Lambert, P., Kumar, A. & Kashanchi, F.(2003). Chromatin remodeling and modification during HIV-1 Tat-activated transcription. Curr HIV Res 1, 343–362.[CrossRef] [Google Scholar]
  77. Ramalingam, S., Kannangai, R., Abraham, O. C., Subramanian, S., Rupali, P., Pulimood, S. A., Jesudason, M. V. & Sridharan, G.(2008). Investigation of apoptotic markers among human immunodeficiency virus (HIV-1) infected individuals. Indian J Med Res 128, 728–733. [Google Scholar]
  78. Richman, D. D., Margolis, D. M., Delaney, M., Greene, W. C., Hazuda, D. & Pomerantz, R. J.(2009). The challenge of finding a cure for HIV infection. Science 323, 1304–1307.[CrossRef] [Google Scholar]
  79. Rohr, O., Marban, C., Aunis, D. & Schaeffer, E.(2003). Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells. J Leukoc Biol 74, 736–749.[CrossRef] [Google Scholar]
  80. Romani, B. & Engelbrecht, S.(2009). Human immunodeficiency virus type 1 Vpr: functions and molecular interactions. J Gen Virol 90, 1795–1805.[CrossRef] [Google Scholar]
  81. Rossi, A., Mukerjee, R., Ferrante, P., Khalili, K., Amini, S. & Sawaya, B. E.(2006). Human immunodeficiency virus type 1 Tat prevents dephosphorylation of Sp1 by TCF-4 in astrocytes. J Gen Virol 87, 1613–1623.[CrossRef] [Google Scholar]
  82. Ruwanpura, S. M., McLachlan, R. I., Stanton, P. G. & Meachem, S. J.(2008). Follicle-stimulating hormone affects spermatogonial survival by regulating the intrinsic apoptotic pathway in adult rats. Biol Reprod 78, 705–713.[CrossRef] [Google Scholar]
  83. Samuel, C. E.(2006). Virus-host interaction minireview series: human immunodeficiency virus, hepatitis C virus, and influenza virus. J Biol Chem 281, 8305–8307.[CrossRef] [Google Scholar]
  84. Sawaya, B. E., Khalili, K., Gordon, J., Taube, R. & Amini, S.(2000). Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates transcription of the viral genome. J Biol Chem 275, 35209–35214.[CrossRef] [Google Scholar]
  85. Scala, G., Ruocco, M. R., Ambrosino, C., Mallardo, M., Giordano, V., Baldassarre, F., Dragonetti, E., Quinto, I. & Venuta, S.(1994). The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein. J Exp Med 179, 961–971.[CrossRef] [Google Scholar]
  86. Schwarze, S. R. & Dowdy, S. F.(2000).In vivo protein transduction: intracellular delivery of biologically active proteins, compounds and DNA. Trends Pharmacol Sci 21, 45–48.[CrossRef] [Google Scholar]
  87. Schwarze, S. R., Ho, A., Vocero-Akbani, A. & Dowdy, S. F.(1999).In vivo protein transduction: delivery of a biologically active protein into the mouse. Science 285, 1569–1572.[CrossRef] [Google Scholar]
  88. Schwarze, S. R., Hurska, K. A. & Dowdy, S. F.(2000). Protein transduction: unrestricted delivery into all cells. Trends Cell Biol 10, 290–295.[CrossRef] [Google Scholar]
  89. Siegelin, M. D., Reuss, D. E., Habel, A., Rami, A. & von-Deimling, A.(2009). Quercetin promotes degradation of survivin and thereby enhances death-receptor-mediated apoptosis in glioma cells. Neuro-oncol 11, 122–131. [Google Scholar]
  90. Sodhi, A., Montaner, S. & Gutkind, J. S.(2004). Viral hijacking of G-protein coupled-receptor signalling networks. Nat Rev Mol Cell Biol 5, 998–1012.[CrossRef] [Google Scholar]
  91. Stettner, M. R., Nance, J. A., Wright, C. A., Kinoshita, Y., Kim, W. K., Morgello, S., Rappaport, J., Khalili, K., Gordon, J. & Johnson, E. M.(2009). SMAD proteins of oligodendroglial cells regulate transcription of JC virus early and late genes coordinately with the Tat protein of human immunodeficiency virus type 1. J Gen Virol 90, 2005–2014.[CrossRef] [Google Scholar]
  92. Subramanian, M., Pilli, T., Bhattacharya, P., Pacini, F., Nikiforov, Y. E., Kanteti, P. V. & Prabhakar, B. S.(2009). Knockdown of IG20 gene expression renders thyroid cancer cells susceptible to apoptosis. J Clin Endocrinol Metab 94, 1467–1471.[CrossRef] [Google Scholar]
  93. Sun, Y., Huang, Y. C., Xu, Q. Z., Wang, H. P., Bai, B., Sui, J. L. & Zhou, P. K.(2006). HIV-1 Tat depresses DNA-PKCs expression and DNA repair, and sensitizes cells to ionizing radiation. Int J Radiat Oncol Biol Phys 65, 842–850.[CrossRef] [Google Scholar]
  94. Tarasenko, T., Kole, H. K., Chi, A. W., Mentink-Kane, M. M., Wynn, T. A. & Bolland, S.(2007). T cell-specific deletion of the inositol phosphatase SHIP reveals its role in regulating Th1/Th2 and cytotoxic responses. Proc Natl Acad Sci U S A 104, 11382–11387.[CrossRef] [Google Scholar]
  95. Tian, R.-r., Liano, Q.-J. & Chen, X.(2008). Prevention and treatment of KSHV-associated diseases with antiviral drugs. Virol Sin 23, 486–495.[CrossRef] [Google Scholar]
  96. Toda, T., Nakamura, M., Morisawa, H. & Hirota, M.(2007). Proteomic identification of oxidative-stress-reporting biomarkers differentially secreted from human neuroblastoma SH-SY5Y cells. J Electrophoresis 51, 21–26.[CrossRef] [Google Scholar]
  97. Toschi, E., Bacigalupo, I., Strippoli, R., Chiozzini, C., Cereseto, A., Falchi, M., Nappi, F., Sgadari, C., Barillari, G. & other authors(2006). HIV-1 Tat regulates endothelial cell cycle progression via activation of the Ras/ERK MAPK signaling pathway. Mol Biol Cell 17, 1985–1994.[CrossRef] [Google Scholar]
  98. Tournier, J. N. & Quesnel-Hellmann, A.(2006). Host-pathogen interactions: a biological rendez-vous of the infectious nonself and danger models. PLoS Pathog 2, E44[CrossRef] [Google Scholar]
  99. Turchan, J., Pocernich, C. B., Gairola, C., Chauhan, A., Schifitto, G., Butterfield, D. A., Buch, S., Narayan, O., Sinai, A. & other authors(2003). Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology 60, 307–314.[CrossRef] [Google Scholar]
  100. Turner, M. A. & Palefsky, J. M.(1998). HIV-1 Tat protein increases invasion of human papillomavirus type 16 positive keratinocytes. J Acquir Immune Defic Syndr 17, A13 [Google Scholar]
  101. Turpin, J. A.(2003). The next generation of HIV/AIDS drugs: novel and developmental anti HIV drugs and targets. Expert Rev Anti Infect Ther 1, 97–128.[CrossRef] [Google Scholar]
  102. Tyagi, M., Rusnati, M., Presta, M. & Giacca, M.(2001). Internalization of HIV-1 Tat requires cell surface heparin sulfate proteoglycans. J Biol Chem 276, 3254–3261.[CrossRef] [Google Scholar]
  103. Vashistha, H., Husain, M., Kumar, D. & Singhal, P. C.(2009). Tubular cell HIV-1 gp120 expression induces caspase 8 activation and apoptosis. Ren Fail 31, 303–312.[CrossRef] [Google Scholar]
  104. Vendeville, A., Rayne, F., Bonhoure, A., Bettache, N., Montcourrier, P. & Beaumelle, B.(2004). HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses. Mol Biol Cell 15, 2347–2360.[CrossRef] [Google Scholar]
  105. Wallace, D. R., Dodson, S. L., Nath, A. & Booze, R. M.(2005). Delta opioid agonists attenuate TAT1–72-induced oxidative stress in SK-N-SH cells. Neurotoxicology 27, 101–107. [Google Scholar]
  106. Westendorp, M. O., Li-Weber, M., Frank, R. W. & Krammeri, P. H.(1994). Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. J Virol 68, 4177–4185. [Google Scholar]
  107. Williams, S. A., Chen, L. F., Kwon, H., Ruiz-Jarabo, C. M., Verdin, E. & Greene, W. C.(2006). NF-κB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J 25, 139–149.[CrossRef] [Google Scholar]
  108. Wong, K., Sharma, A., Awasthi, S., Matlock, E. F., Rogers, L., Lint, C. V., Skiest, D. J., Burns, D. K. & Harrod, R.(2005). HIV-1 Tat interactions with p300 and PCAF transcriptional coactivators inhibit histone acetylation and neurotrophin signaling through CREB. J Biol Chem 280, 9390–9399.[CrossRef] [Google Scholar]
  109. Yedavalli, V. S. R. K., Benkirane, M. & Jeang, K. T.(2003). Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by human and murine cyclin T1 requires Sp1. J Biol Chem 278, 6404–6410.[CrossRef] [Google Scholar]
  110. Zagury, D., Lachgar, A., Chams, V., Fall, L. S., Bernard, J., Zagury, J. F., Bizzini, B., Gringeri, A., Santagostini, E. & other authors(1998). Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C–C chemokine decline in AIDS. Proc Natl Acad Sci U S A 95, 3851–3856.[CrossRef] [Google Scholar]
  111. Zauli, G., Milani, D., Mirandola, P., Mazzoni, M., Secchiero, P., Miscia, S. & Capitani, S.(2001). HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/AKT/cyclic nucleoside phosphodiesterase pathway. FASEB J 15, 483–491.[CrossRef] [Google Scholar]
  112. Zhang, M., Li, X., Pang, X., Ding, L., Wood, O., Clouse, K. A., Hewlett, I. & Dayton, A. I.(2002). Bcl-2 upregulation by HIV-1 Tat during infection of primary human macrophages in culture. J Biomed Sci 9, 133–139.[CrossRef] [Google Scholar]
  113. Zhao, T., Adams, M. H., Zou, S. P., El-Hage, N., Hauser, K. F. & Knapp, P. E.(2007). Silencing the PTEN gene is protective against neuronal death induced by human immunodeficiency virus type 1 Tat. J Neurovirol 13, 97–106.[CrossRef] [Google Scholar]
  114. Zheng, L., Yang, Y. D., Lu, G. C. & Salvato, M. S.(2005). Extracellular HIV Tat and Tat cysteine rich peptide increase CCR5 expression in monocytes. J Zhejiang Univ Sci B 6, 668–672. [Google Scholar]
  115. Zheng, L., Yang, Y., Guocai, L., Pauza, C. D. & Salvato, M. S.(2007). HIV Tat protein increases Bcl-2 expression in monocytes which inhibits monocyte apoptosis induced by tumor necrosis factor-alpha-related apoptosis-induced ligand. Intervirology 50, 224–228.[CrossRef] [Google Scholar]
  116. Zhou, M., Deng, L., Kashanchi, F., Brady, J. N., Shatkin, A. J. & Kumar, A.(2003). The Tat/TAR-dependent phosphorylation of RNA polymerase II C-terminal domain stimulates cotranscriptional capping of HIV-1 mRNA. Proc Natl Acad Sci U S A 100, 12666–12671.[CrossRef] [Google Scholar]
  117. Zuo, Y., Matsusaka, T., Zhong, J., Ma, J., Ma, L. J., Hanna, Z., Jolicoeur, P., Fogo, A. B. & Ichikawa, I.(2006). HIV-1 genes vpr and nef synergistically damage podocytes, leading to glomerulosclerosis. J Am Soc Nephrol 17, 2832–2843.[CrossRef] [Google Scholar]
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