HIV-1 Tat mediates degradation of RON receptor tyrosine kinase, a regulator of inflammation

Journal of Immunology

Volumn 181, Issue 2, 2008, Pages 1548-1555

  Kalantari, Parisa ^a   Harandi, Omid F ^b   Hankey, Pamela A ^a   Henderson, Andrew J ^a,c  

^a PENNSYLVANIA STATE UNIVERSITY   (United States)

^b PENNSYLVANIA STATE UNIVERSITY   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD14 ANTIGEN; CELL SURFACE RECEPTOR; INTERCELLULAR ADHESION MOLECULE 1; PROTEIN TYROSINE KINASE A; TRANSACTIVATOR PROTEIN; TRANSFERRIN RECEPTOR; TYROSINE KINASE RECEPTOR; UBIQUITIN; PROTEASOME; PROTEIN TYROSINE KINASE; RON PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ARTICLE; CELL SURFACE; DISEASE COURSE; DOWN REGULATION; EMBRYO; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFLAMMATION; MICROENVIRONMENT; MONOCYTE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; VIRUS REPLICATION; VIRUS TRANSCRIPTION; CELL LINE; CELL STRAIN U937; CHEMISTRY; GENE VECTOR; GENETIC TRANSFECTION; IMMUNOLOGY; MACROPHAGE; METABOLISM; PROTEIN TERTIARY STRUCTURE; VIROLOGY;

CELL LINE; GENETIC VECTORS; HIV-1; HUMANS; INFLAMMATION; MACROPHAGES; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN STRUCTURE, TERTIARY; RECEPTOR PROTEIN-TYROSINE KINASES; TAT GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; TRANSFECTION; U937 CELLS; UBIQUITIN;

EID: 49049117006     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.181.2.1548     Document Type: Article

References (80)

1. Gendelman, H. E., J. M. Orenstein, L. M. Baca, B. Weiser, H. Burger, D. C. Kalter, and M. S. Meltzer. 1989. The macrophage in the persistence and pathogenesis of HIV infection. AIDS 3: 475-495. (Pubitemid 19231898)
2. Koenig, S., H. E. Gendelman, J. M. Orenstein, M. C. Dal Canto, G. H. Pezeshkpour, M. Yungbluth, F. Janotta, A. Aksamit, M. A. Martin, and A. S. Fauci. 1986. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science 233: 1089-1093. (Pubitemid 16032241)
3. Gartner, S., P. Markovits, D. M. Markovitz, M. H. Kaplan, R. C. Gallo, and M. Popovic. 1986. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233: 215-219. (Pubitemid 16008118)
4. Giulian, D., K. Vaca, and C. A. Noonan. 1990. Secretion of neurotoxins by mononuclear phagocytes infected with HIV-1. Science 250: 1593-1596. (Pubitemid 120034376)
5. Ploegh, H. L. 1998. Viral strategies of immune evasion. Science 280: 248-253.
6. Emerman, M., and M. H. Malim. 1998. HIV-1 regulatory/accessory genes: keys to unraveling viral and host cell biology. Science 280: 1880-1884. (Pubitemid 28299384)
7. Howcroft, T. K., K. Strebel, M. A. Martin, and D. S. Singer. 1993. Repression of MHC class I gene promoter activity by two-exon Tat of HIV. Science 260: 1320-1322. (Pubitemid 23231975)
8. Weissman, J. D., J. A. Brown, T. K. Howcroft, J. Hwang, A. Chawla, P. A. Roche, L. Schiltz, Y. Nakatani, and D. S. Singer. 1998. HIV-1 tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes. Proc. Natl. Acad. Sci. USA 95: 11601-11606. (Pubitemid 28460461)
9. Caldwell, R. L., B. S. Egan, and V. L. Shepherd. 2000. HIV-1 Tat represses transcription from the mannose receptor promoter. J. Immunol. 165: 7035-7041.
10. Carroll, I. R., J. Wang, T. K. Howcroft, and D. S. Singer. 1998. HIV Tat represses transcription of the β2-microglobulin promoter. Mol. Immunol. 35: 1171-1178. (Pubitemid 29151778)
11. Dayton, A. I., E. F. Terwilliger, J. Potz, M. Kowalski, J. G. Sodroski, and W. A. Haseltine. 1988. Cis-acting sequences responsive to the rev gene product of the human immunodeficiency virus. J. Acquired Immune Defic. Syndr. 1: 441-452. (Pubitemid 19129851)
12. Fisher, A. G., M. B. Feinberg, S. F. Josephs, M. E. Harper, L. M. Marselle, G. Reyes, M. A. Gonda, A. Aldovini, C. Debouk, R. C. Gallo, et al. 1986. The trans-activator gene of HTLV-III is essential for virus replication. Nature 320: 367-371. (Pubitemid 16077280)
13. Berkhout, B., R. H. Silverman, and K. T. Jeang. 1989. Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell 59: 273-282. (Pubitemid 19264373)
14. Berkhout, B., A. Gatignol, A. B. Rabson, and K. T. Jeang. 1990. TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. Cell 62: 757-767. (Pubitemid 20275715)
15. Zhou, M., M. A. Halanski, M. F. Radonovich, F. Kashanchi, J. Peng, D. H. Price, and J. N. Brady. 2000. Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription. Mol. Cell. Biol. 20: 5077-5086. (Pubitemid 30431561)
16. Dingwall, C., I. Ernberg, M. J. Gait, S. M. Green, S. Heaphy, J. Karn, A. D. Lowe, M. Singh, M. A. Skinner, and R. Valerio. 1989. Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro. Proc. Natl. Acad. Sci. USA 86: 6925-6929. (Pubitemid 19240844)
17. Sabatier, J. M., E. Vives, K. Mabrouk, A. Benjouad, H. Rochat, A. Duval, B. Hue, and E. Bahraoui. 1991. Evidence for neurotoxic activity of tat from human immunodeficiency virus type 1. J. Virol. 65: 961-967.
18. Subramanyam, M., W. G. Gutheil, W. W. Bachovchin, and B. T. Huber. 1993. Mechanism of HIV-1 Tat induced inhibition of antigen-specific T cell responsiveness. J. Immunol. 150: 2544-2553. (Pubitemid 23127501)
19. Viscidi, R. P., K. Mayur, H. M. Lederman, and A. D. Frankel. 1989. Inhibition of antigen-induced lymphocyte proliferation by Tat protein from HIV-1. Science 246: 1606-1608.
20. Lafrenie, R. M., L. M. Wahl, J. S. Epstein, K. M. Yamada, and S. Dhawan. 1997. Activation of monocytes by HIV-Tat treatment is mediated by cytokine expression. J. Immunol. 159: 4077-4083.
21. Buonaguro, L., G. Barillari, H. K. Chang, C. A. Bohan, V. Kao, R. Morgan, R. C. Gallo, and B. Ensoli. 1992. Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. J. Virol. 66: 7159-7167.
22. Buonaguro, L., F. M. Buonaguro, G. Giraldo, and B. Ensoli. 1994. The human immunodeficiency virus type 1 Tat protein transactivates tumor necrosis factor β gene expression through a TAR-like structure. J. Virol. 68: 2677-2682. (Pubitemid 24091947)
23. Puri, R. K., and B. B. Aggarwal. 1992. Human immunodeficiency virus type 1 tat gene up-regulates interleukin 4 receptors on a human B-lymphoblastoid cell line. Cancer Res. 52: 3787-3790.
24. Sastry, K. J., H. R. Reddy, R. Pandita, K. Totpal, and B. B. Aggarwal. 1990. HIV-1 tat gene induces tumor necrosis factor-β (lymphotoxin) in a human Blymphoblastoid cell line. J. Biol. Chem. 265: 20091-20093.
25. Scala, G., M. R. Ruocco, C. Ambrosino, M. Mallardo, V. Giordano, F. Baldassarre, E. Dragonetti, I. Quinto, and S. Venuta. 1994. The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein. J. Exp. Med. 179: 961-971. (Pubitemid 24065654)
26. Weiss, J. M., A. Nath, E. O. Major, and J. W. Berman. 1999. HIV-1 Tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood-brain barrier and up-regulates CCR5 expression on human monocytes. J. Immunol. 163: 2953-2959.
27. Secchiero, P., D. Zella, S. Capitani, R. C. Gallo, and G. Zauli. 1999. Extracellular HIV-1 tat protein up-regulates the expression of surface CXC-chemokine receptor 4 in resting CD4+ T cells. J. Immunol. 162: 2427-2431. (Pubitemid 29288872)
28. Sharma, V., M. Xu, L. M. Ritter, and N. M. Wilkie. 1996. HIV-1 tat induces the expression of a new hematopoietic cell-specific transcription factor and downregulates MIP-1α gene expression in activated T-cells. Biochem. Biophys. Res. Commun. 223: 526-533. (Pubitemid 26246106)
29. Zhang, M., J. Drenkow, C. S. Lankford, D. M. Frucht, R. L. Rabin, T. R. Gingeras, C. Venkateshan, F. Schwartzkopff, K. A. Clouse, and A. I. Dayton. 2006. HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in human macrophages in vitro. J. Leukocyte Biol. 79: 1328-1338. (Pubitemid 44835568)
30. Husain, S. R., P. Leland, B. B. Aggarwal, and R. K. Puri. 1996. Transcriptional up-regulation of interleukin 4 receptors by human immunodeficiency virus type 1 tat gene. AIDS Res. Hum. Retroviruses 12: 1349-1359. (Pubitemid 26336862)
31. Albini, A., R. Soldi, D. Giunciuglio, E. Giraudo, R. Benelli, L. Primo, D. Noonan, M. Salio, G. Camussi, W. Rockl, and F. Bussolino. 1996. The angiogenesis induced by HIV-1 tat protein is mediated by the Flk-1/KDR receptor on vascular endothelial cells. Nat. Med. 2: 1371-1375. (Pubitemid 26401742)
32. Zocchi, M. R., A. Poggi, and A. Rubartelli. 1997. The RGD-containing domain of exogenous HIV-1 Tat inhibits the engulfment of apoptotic bodies by dendritic cells. AIDS 11: 1227-1235.
33. Jones, K. A. 1997. Taking a new TAK on tat transactivation. Genes Dev. 11: 2593-2599.
34. Ronsin, C., F. Muscatelli, M. G. Mattei, and R. Breathnach. 1993. A novel putative receptor protein tyrosine kinase of the met family. Oncogene 8: 1195-1202. (Pubitemid 23129841)
35. Correll, P. H., A. C. Morrison, and M. A. Lutz. 2004. Receptor tyrosine kinases and the regulation of macrophage activation. J. Leukocyte Biol. 75: 731-737. (Pubitemid 38580051)
36. Ghigna, C., S. Giordano, H. Shen, F. Benvenuto, F. Castiglioni, P. M. Comoglio, M. R. Green, S. Riva, and G. Biamonti. 2005. Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol. Cell 20: 881-890. (Pubitemid 41814877)
37. Lutz, M. A., and P. H. Correll. 2003. Activation of CR3-mediated phagocytosis by MSP requires the RON receptor, tyrosine kinase activity, phosphatidylinositol 3-kinase, and protein kinase Cζ. J. Leukocyte Biol. 73: 802-814. (Pubitemid 38040459)
38. Wang, M. H., G. W. Cox, T. Yoshimura, L. A. Sheffler, A. Skeel, and E. J. Leonard. 1994. Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages. J. Biol. Chem. 269: 14027-14031. (Pubitemid 24191155)
39. Chen, Y. Q., J. H. Fisher, and M. H. Wang. 1998. Activation of the RON receptor tyrosine kinase inhibits inducible nitric oxide synthase (iNOS) expression by murine peritoneal exudate macrophages: phosphatidylinositol-3 kinase is required for RON-mediated inhibition of iNOS expression. J. Immunol. 161: 4950-4959.
40. Liu, Q. P., K. Fruit, J. Ward, and P. H. Correll. 1999. Negative regulation of macrophage activation in response to IFN-γ and lipopolysaccharide by the STK/ RON receptor tyrosine kinase. J. Immunol. 163: 6606-6613.
41. Morrison, A. C., C. B. Wilson, M. Ray, and P. H. Correll. 2004. Macrophagestimulating protein, the ligand for the stem cell-derived tyrosine kinase/RON receptor tyrosine kinase, inhibits IL-12 production by primary peritoneal macrophages stimulated with IFN-γ and lipopolysaccharide. J. Immunol. 172: 1825-1832.
42. Morrison, A. C., and P. H. Correll. 2002. Activation of the stem cell-derived tyrosine kinase/RON receptor tyrosine kinase by macrophage-stimulating protein results in the induction of arginase activity in murine peritoneal macrophages. J. Immunol. 168: 853-860.
43. Correll, P. H., A. Iwama, S. Tondat, G. Mayrhofer, T. Suda, and A. Bernstein. 1997. Deregulated inflammatory response in mice lacking the STK/RON receptor tyrosine kinase. Genes Funct. 1: 69-83.
44. Leonis, M. A., K. Toney-Earley, S. J. Degen, and S. E. Waltz. 2002. Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin- induced acute liver failure. Hepatology 36: 1053-1060.
45. Tsutsui, S., F. Noorbakhsh, A. Sullivan, A. J. Henderson, K. Warren, K. Toney-Earley, S. E. Waltz, and C. Power. 2005. RON-regulated innate immunity is protective in an animal model of multiple sclerosis. Ann. Neurol. 57: 883-895. (Pubitemid 40798627)
46. Lutz, M. A., F. Gervais, A. Bernstein, A. L. Hattel, and P. H. Correll. 2002. STK receptor tyrosine kinase regulates susceptibility to infection with Listeria monocytogenes. Infect. Immun. 70: 416-418. (Pubitemid 34028645)
47. Lee, E. S., P. Kalantari, S. Tsutsui Section, A. Klatt, J. Holden, P. H. Correll, C. Power Section, and A. J. Henderson. 2004. RON receptor tyrosine kinase, a negative regulator of inflammation, inhibits HIV-1 transcription in monocytes/ macrophages and is decreased in brain tissue from patients with AIDS. J. Immunol. 173: 6864-6872.
48. Klatt, A., Z. Zhang, P. Kalantari, P. A. Hankey, D. S. Gilmour, and A. J. Henderson. 2008. The receptor tyrosine kinase RON represses HIV-1 transcription by targeting RNA polymerase II processivity. J. Immunol. 180: 1670-1677.
49. + T cells. Proc. Natl. Acad. Sci. USA 94: 8714-8719.
50. Wei, X., L. Hao, S. Ni, Q. Liu, J. Xu, and P. H. Correll. 2005. Altered exon usage in the juxtamembrane domain of mouse and human RON regulates receptor activity and signaling specificity. J. Biol. Chem. 280: 40241-40251. (Pubitemid 41779162)
51. Herrmann, C. H., and A. P. Rice. 1995. Lentivirus Tat proteins specifically associate with a cellular protein kinase, TAK, that hyperphosphorylates the carboxyl- terminal domain of the large subunit of RNA polymerase II: candidate for a Tat cofactor. J. Virol. 69: 1612-1620.
52. Sadaie, M. R., J. Rappaport, T. Benter, S. F. Josephs, R. Willis, and F. Wong-Staal. 1988. Missense mutations in an infectious human immunodefi- ciency viral genome: functional mapping of tat and identification of the rev splice acceptor. Proc. Natl. Acad. Sci. USA 85: 9224-9228.
53. Gao, F., Y. Li, J. M. Decker, F. W. Peyerl, F. Bibollet-Ruche, C. M. Rodenburg, Y. Chen, D. R. Shaw, S. Allen, R. Musonda, et al. 2003. Codon usage optimization of HIV type 1 subtype C gag, pol, env, and nef genes: in vitro expression and immune responses in DNA-vaccinated mice. AIDS Res. Hum. Retroviruses 19: 817-823. (Pubitemid 37215137)
54. Connor, R. I., K. E. Sheridan, C. Lai, L. Zhang, and D. D. Ho. 1996. Characterization of the functional properties of env genes from long-term survivors of human immunodeficiency virus type 1 infection. J. Virol. 70: 5306-5311.
55. Pear, W. S., G. P. Nolan, M. L. Scott, and D. Baltimore. 1993. Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA 90: 8392-8396. (Pubitemid 23277674)
56. Bohan, C. A., F. Kashanchi, B. Ensoli, L. Buonaguro, K. A. Boris-Lawrie, and J. N. Brady. 1992. Analysis of Tat transactivation of human immunodeficiency virus transcription in vitro. Gene Expression 2: 391-407.
57. Ensoli, B., G. Barillari, S. Z. Salahuddin, R. C. Gallo, and F. Wong-Staal. 1990. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature 345: 84-86. (Pubitemid 20152458)
58. Ensoli, B., L. Buonaguro, G. Barillari, V. Fiorelli, R. Gendelman, R. A. Morgan, P. Wingfield, and R. C. Gallo. 1993. Release, uptake, and effects of extracellular human immunodeficiency virus type 1 Tat protein on cell growth and viral transactivation. J. Virol. 67: 277-287. (Pubitemid 23002988)
59. Fujinaga, K., R. Taube, J. Wimmer, T. P. Cujec, and B. M. Peterlin. 1999. Interactions between human cyclin T, Tat, and the transactivation response element (TAR) are disrupted by a cysteine to tyrosine substitution found in mouse cyclin T. Proc. Natl. Acad. Sci. USA 96: 1285-1290. (Pubitemid 29098443)
60. Penengo, L., C. Rubin, Y. Yarden, and G. Gaudino. 2003. c-Cbl is a critical modulator of the Ron tyrosine kinase receptor. Oncogene 22: 3669-3679. (Pubitemid 36760729)
61. Hammond, D. E., S. Urbe, G. F. Vande Woude, and M. J. Clague. 2001. Downregulation of MET, the receptor for hepatocyte growth factor. Oncogene 20: 2761-2770. (Pubitemid 32549833)
62. Hammond, D. E., S. Carter, and M. J. Clague. 2004. Met receptor dynamics and signalling. Curr. Top. Microbiol. Immunol. 286: 21-24.
63. Hart, P. D., and M. R. Young. 1991. Ammonium chloride, an inhibitor of phagosome- lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. J. Exp. Med. 174: 881-889.
64. Rice, A. P., and F. Carlotti. 1990. Mutational analysis of the conserved cysteinerich region of the human immunodeficiency virus type 1 Tat protein. J. Virol. 64: 1864-1868. (Pubitemid 20104933)
65. Sodroski, J., C. Rosen, F. Wong-Staal, S. Z. Salahuddin, M. Popovic, S. Arya, R. C. Gallo, and W. A. Haseltine. 1985. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science 227: 171-173. (Pubitemid 15154221)
66. Swigut, T., N. Shohdy, and J. Skowronski. 2001. Mechanism for down-regulation of CD28 by Nef. EMBO J. 20: 1593-1604.
67. Blagoveshchenskaya, A. D., M. J. Hannah, S. Allen, and D. F. Cutler. 2002. Selective and signal-dependent recruitment of membrane proteins to secretory granules formed by heterologously expressed von Willebrand factor. Mol. Biol. Cell 13: 1582-1593.
68. De, S. K., C. N. Venkateshan, P. Seth, D. C. Gajdusek, and C. J. Gibbs. 1998. Adenovirus-mediated human immunodeficiency virus-1 Nef expression in human monocytes/macrophages and effect of Nef on down-modulation of Fcγ receptors and expression of monokines. Blood 91: 2108-2117.
69. Frankel, A. D., and C. O. Pabo. 1988. Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55: 1189-1193. (Pubitemid 19020071)
70. Aprea, S., L. Del Valle, G. Mameli, B. E. Sawaya, K. Khalili, and F. Peruzzi. 2006. Tubulin-mediated binding of human immunodeficiency virus-1 Tat to the cytoskeleton causes proteasomal-dependent degradation of microtubule-associated protein 2 and neuronal damage. J. Neurosci. 26: 4054-4062. (Pubitemid 44315426)
71. Seeger, M., K. Ferrell, R. Frank, and W. Dubiel. 1997. HIV-1 tat inhibits the 20 S proteasome and its 11 S regulator-mediated activation. J. Biol. Chem. 272: 8145-8148. (Pubitemid 27147763)
72. Apcher, G. S., S. Heink, D. Zantopf, P. M. Kloetzel, H. P. Schmid, R. J. Mayer, and E. Kruger. 2003. Human immunodeficiency virus-1 Tat protein interacts with distinct proteasomal α and β subunits. FEBS Lett. 553: 200-204. (Pubitemid 37206351)
73. Jeffers, M., G. A. Taylor, K. M. Weidner, S. Omura, and G. F. Vande Woude. 1997. Degradation of the Met tyrosine kinase receptor by the ubiquitin-proteasome pathway. Mol. Cell. Biol. 17: 799-808. (Pubitemid 27044379)
74. Jeang, K. T., Y. Chang, B. Berkhout, M. L. Hammarskjold, and D. Rekosh. 1991. Regulation of HIV expression: mechanisms of action of Tat and Rev. AIDS 5 (Suppl. 2): S3-S14.
75. Jones, K. A., and B. M. Peterlin. 1994. Control of RNA initiation and elongation at the HIV-1 promoter. Annu. Rev. Biochem. 63: 717-743.
76. Dayton, A. I., J. G. Sodroski, C. A. Rosen, W. C. Goh, and W. A. Haseltine. 1986. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell 44: 941-947.
77. Arya, S. K., C. Guo, S. F. Josephs, and F. Wong-Staal. 1985. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science 229: 69-73. (Pubitemid 15227242)
78. Alcami, J., T. Lain de Lera, L. Folgueira, M. A. Pedraza, J. M. Jacque, F. Bachelerie, A. R. Noriega, R. T. Hay, D. Harrich, R. B. Gaynor, et al. 1995. Absolute dependence on κB responsive elements for initiation and Tat-mediated amplification of HIV transcription in blood CD4 T lymphocytes. EMBO J. 14: 1552-1560.
79. Bagasra, O., K. Khalili, T. Seshamma, J. P. Taylor, and R. J. Pomerantz. 1992. TAR-independent replication of human immunodeficiency virus type 1 in glial cells. J. Virol. 66: 7522-7528.
80. Taylor, J. P., R. Pomerantz, O. Bagasra, M. Chowdhury, J. Rappaport, K. Khalili, and S. Amini. 1992. TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J. 11: 3395-3403.