Abstract
Discovery of the link between human T-cell leukemia virus type I (HTLV-I) and adult T-cell leukemia, and the emergence of the acquired immunodeficiency syndrome, in association with human immunodeficiency virus type 1 (HIV-1) has led to intense investigation of underlying mechanisms of pathogenesis and retroviral gene regulation. In contrast to avian and murine RNA viruses previously studied, the human oncogenic retroviruses HTLV-I/II, as well as the Lentivirus family, represented by HIV-1, HIV-2, and SIV, demonstrated genomes of increased complexity, encoding multiple mRNA species in contrast to the simpler avian/murine species. “Simple” retroviruses generally encode two mRNA species, unspliced gag/pol, and singly spliced env mRNA, while additional splicing events result in as many as eight identifiable mRNA species for HTLV-1, encoding at least two, and potentially up to five, additional proteins (Myers and Pavlakis 1991). For HIV-1, an exceptionally complex pattern of transcripts is observed, resulting in up to 20 different mRNAs and ten or more different proteins (Myers and Pavlakis 1991; Schwartz et al. 1990). Several of the proteins encoded by the novel spliced mRNAs in HTLV-I/II and HIV-1/HIV-2 act as regulators, both transcriptional and posttranscriptional, of viral gene expression. By definition, these trans-acting regulatory proteins interact with both cis-acting viral sequences, as well as with cellular regulatory machinery to alter viral gene expression. Researchers have therefore focused attention on possible cellular regulatory consequences of retro-viral gene expression.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alexandre C, Charnay P, Verier B (1991) Transactivation of krox-20 and krox-24 promoters by the HTLV-I Tax protein through common regulatory elements. Oncogene 6: 1851–1857
Allison ET, Drucker DJ (1992) Parathyroid hormone-like peptide shares features with members of the early response gene family: rapid induction by serum, growth factors, and cycloheximide. Cancer Res 2: 103
Ames RS, Holskin B, Mitcho M, Shalloway D, Chen MJ (1990) Induction of sensitivity to the cytotoxic action of tumor necrosis factor alpha by adenovirus E1A is independent of transformation and transcriptional activation. J Virol 64: 4115–4122
Aoyama N, Nagase T, Sawazaki T, Mizuguchi G, Nakagoshi H, Fujisawa JI, Yoshida M, Ishii S (1992) Overlap of the p53-responsive element and cAMP-responsive element in the enhancer of human T-cell leukemia virus type I. Proc Natl Acad Sci USA 89: 5403-5407
Arima N, Molitor JA, Smith MR, Kim JH, Daitoku Y, Greene WC (1991) Human T-cell leukemia virus type I Tax induces expression of the Rel-related family of kappa B enhancer-binding proteins: evidence for a pretranslational component of regulation. J Virol 65: 6892–6899
Ballard DW, Boehnlein E, Lowenthal JS, Wano Y, Franza BR, Greene WC (1988) HTLV-1I Tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha-gene. Science 241: 1652–1655
Ballard DW, Boehnlein E, Hoffman JA, Bogerd HP, Dixon EP, Franza BR, Greene WC (1989) Activation of the IL-2 receptor alpha gene: regulatory role for DNA-protein interactions flanking the kappa B enhancer. New Biologist 1: 83–92
Barillari G, Buonaguro L, Fiorelli V, Hoffman J, Michaels F, Gallo RC, Ensoli B (1992) Effects of cytokines from activated immune cells on vascular cell growth and HIV-1 gene expression: implications for AIDS-Kaposi’s sarcoma pathogenesis. J Immunol 149: 3727–3734
Beimling P, Moelling K (1989) Isolation and characterization of the Tax protein of HTLV-I. Oncogene 4: 511–516
Benjouad A, Mabrouk K, Moulard M, Gluckman JC, Rochat H, Van Rietschoten J, Sabatier JM (1993) Cytotoxic effect on lymphocytes of Tat from human immunodeficiency virus (HIV-1). FEBS Lett 319: 119–124
Beraud C, Lombard-Platet G, Michal Y, Jalinot P (1991) Binding of the HTLV-I Tax-1 transactivator to the inducible 21-bp enhancer is mediated by the cellular factor HEB-1. EMBO J 10: 3795–3803
Berger JR, Svenningson A, Raffanti S, Resnick L (1991) Tropical spastic paraparesis-like illness occurring in a patient dually infected with HIV-1 and HTLV-II. Neurology 41: 85–87
Black AC, Arrigo SJ, Ruland CT, Allogiamento T, Chin E, Chen ISY, Rosenblatt JD (1991a) Regulation of HTLV-II gene expression by Rex involves positive and negative cis-acting elements in the 5′ long terminal repeat. Virology 181: 433–444
Black AC, Ruland CT, Yip MT, Luo J, Tran B, Kalsi A, Quan E, Aboud M, Chen ISY, Rosenblatt JD (1991b) Human T-cell leukemia virus type II Rex binding and activity require an intact splice donor site and a specific RNA secondary structure. J Virol 65: 6645–6653
Bohnlein E, Lowenthal JW, Seibevitz M, Ballard DW, Franza BR, Greene WC (1988) The same inducible nuclear protein regulates mitogen activation of both the interleukin-2 receptor alpha gene and type 1 HIV. Cell 53: 827–836
Bohnlein E, Lowenthal JW, Wano Y, Franza BR, Ballard DW, Greene WC (1989) HIV-1, HTLV-I and the IL-2 receptor: insights into transcriptional control. Hamatol Bluttransfus 32: 393–401.
Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF (1988) Humoral hypercalcemia of cancer: identification of a novel parathyroid hormone-like peptide. N Engl J Med 319: 556–563
Buonaguro L, Barillari G, Chang HK, Bohan CA, Kao V, Morgan R, Gallo RC, Ensoli B (1992) Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. J Virol 66: 7159–7167
Cann AJ, Rosenblatt JD, Wachsman W (1985) Identification of the gene responsible for human T-cell leukemia virus transcriptional regulation. Nature 318: 571–574
Chen ISY, McLaughlin J, Gasson JC, Clark SC, Golde DW (1983a) Molecular characterization of genome of a novel human T-cell leukemia virus. Nature 305: 502–505.
Chen ISY, Quan SG, Golde DW (1983b) Human T-cell leukemia virus type II transforms normal human lymphocytes. Proc Natl Acad Sci USA 80: 7006–7009
Chen ISY, Slamon DJ, Rosenblatt JD, Shah NP, Quan SG, Wachsman W (1985) The x gene is essential for HTLV replication. Science 229: 54–58
Chen H, Boyle TJ, Lyerly HK (1992) Interleukin-6 expression is not regulated by HIV-1 protein Tat. Int Conf AIDS 8: A77
Chowdhury M, Taylor JP, Tada H, Rappaport J, Wong-Staal F, Amini S, Khalili K (1990). Regulation of the human neurotropic virus promoter by JCV-T antigen and HIV-1 Tat protein. Oncogene 5: 1737–1742
Chowdhury M, Kundu M, Khalili K (1993) GA/GC-rich sequence confers Tat responsiveness to human neurotropic virus promoter, JCVL, in cells derived from central nervous system. Oncogene 8: 887–892
Cross SL, Feinberg MB, Wolf JB et al (1987) Regulation of the human interleukin-2 receptor chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell 49:47–56
Cullen BR (1990) The HIV-1 Tat protein: an RNA sequence-specific processivity factor. Cell 63: 655–657
Depper JM, Leonard WJ, Kronke M (1984) Augmented T-cell growth factor receptor expression in HTLV-I-infected human leukemic T cells. J Immunol 133: 1691–1695
Di Luca, D, Secchiero P, Bovenzi P, et al. (1991) Reciprocal in vitro interactions between human herpes virus-6 and HIV-1 Tat. AIDS 5: 1095–1098
Drucker DJ, Asa SL, Henerson J, Goltzman D (1989) The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas. Mol Endocrinol 3: 1589–1595
Duyao MP, Kessler DJ, Spicer DB, Bartholomew C, Cleveland JL, Siekevitz M, Sonenshein GE (1992) Transactivation of the c-myc promoter by human T-cell leukemia virus type I Tax is mediated by NF kappa B. J Biol Chem 267: 16288`–16291
Ejima E, Rosenblatt JD, Massari M, Quan E, Stephens D, Rosen CA, Prager D (1993) Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type 1 (HTLV-I) fax and HTLV-II Tax proteins. Blood 81: 1017–1024.
Elovaara I, Koenig S, Brewah AY, Woods RM, Lekhy T, Jacobson S (1993) High human T-cell lymphotropic virus type I (HTLV-I)-specific precursor cytotoxic T-lymphocyte frequencies in patients with HTLV-I-associated neurological disease. J Exp Med 177: 1567–1573
Ensoli B, Nakamura S, Salahuddin SZ, Biberfeld P, Larsson L, Beaver B, Wong-Staal F, Gallo RC (1989). AIDS-Kaposi’s sarcoma-derived cells express cytokines with autocrine and paracrine growth effects. Science 243: 223`–226
Ensoli B, Barillari G, Salahuddin SZ, Gallo RC, Wong-Staal F (1990). Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients. Nature 345: 84–86
Ensoli B, Barillari G, Buonaguro L, Gallo RC (1991) Molecular mechanisms in the pathogenesis of AIDS-associated Kaposi’s sarcoma. Adv Exp Med Biol 303: 27–38
Ensoli B,Buonaguro L, Barillari G, Fiorelli V, Gendelman R, Morgan RA, Wingfield, P, Gallo RC (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
Felber BK, Paskalis H, Kleinman-Ewing C, Wong-Staal F, Pavalis GN (1985) The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science 229: 675-679
Fujii M, Sassone-Corsi P, Verma IM (1988) c-fos promoter transactivation by the Tax-1 protein of human T-cell leukemic virus type 1. Proc Natl Acad Sci USA 85: 8526-8530
Fujii M, Tsuchiya H, Seiki M (1991) HTLV-1 Tax has distinct but overlapping domains for transcriptional activation and for enhancer specificity. Oncogene 6: 2349-2352
Fujii M, Tsuchiya H, Chuhjo T, Akizawa T, Seiki M (1992) Interaction of HTLV-I Tax 1 with p67SRF causes the abberrant induction of cellular immediate early genes through CArG boxes. Genes Dev 6: 2066–2076
Fujisawa J, Toita M, Yoshimura T, Yoshida M (1991) The indirect association of human T-cell leukemia virus Tax protein with DNA results in transcriptional activation. J Virol 65: 4525–4528
Gazzolo L, Duc Dodon M (1991) Molecular and cellular events at the onset of the lymphoproliferative process induced by HTLV-I. Bull Cancer 78: 291–298
Gessain A, Berin F, Vernant JC, Gout O, Maurs L, Calendar A, de The G (1985) Antibodies to human T-lymphotropic virus type I in patients with tropical spastic paraparesis. Lancet 2: 407–410
Giam CZ, Xu YL (1989) HTLV-I Tax gene product activates transcription via preexisting cellular factors and cAMP responsive element. J Biol Chem 264: 15236–15241
Goltzman D, Hendy GN, Banville D (1989) Parathyroid hormone-like peptide: molecular characterization and biological properties. Elsevier, Amsterdam, pp 39–44
Grassman R, Berchtold S, Aepinus C, Ballaun C, Boehnlein Z, Fleckenstein B (1991) In vitro binding of human T-cell leukemia virus Rex proteins to the Rex response element of viral transcripts. J Virol 65: 3721–3727
Green JE, Begley CG, Wagner DK, Waldmann TA, Jay G (1989) Transactivation of GM-CSF and the IL-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 Tax gene. Mol Cell Biol 9: 4731–4737
Green PL, Chen ISY (1990) Regulation of human T-cell leukemia virus expression. FASEB J 4: 169–175
Green PL, Xie YM, Chen ISY (1991) The Rex proteins of human T-cell leukemia virus type II differ by sirine phosphorylation. J Virol 65: 546–550
Greene WC (1986) The human interleukin-2 receptor: normal and abnormal expression in T cells and in leukemias induced by the human T-lymphotropic retroviruses. Ann Intern Med 105: 560–572
Greene WC (1990) Regulation of HIV-1 gene expression. Annu Rev Immunol 8: 453–475
Greene WC, Bohnlein E, Ballard DW (1989) HIV-I, HTLV-I and normal T-cell growth: transcriptional strategies and surprises. Immunol Today 10: 272–278
Gutekunst KA, Kashanchi F, Brady JN, Bednarik DP (1993) Transcription of the HIV-1 LTR is regulated by the density of DNA CpG methylation. J Acquir Immune Defic Syndr 6: 541–559
Hayman M, Arbuthnott G, Harkiss G, Brace H, Filippi P, Philippon V, Thomson D, Vigne R, Wright A (1993) Neurotoxicity of peptide analogues of the transactivating protein Tat from Maedi-Visna virus and human immunodeficiency virus. Neuroscience 53: 1–6
Heiland DE, Welles JL, Caputo A, Haseltine WA (1991) Transcellular transactivation by the human immunodeficiency virus type 1 Tat protein. J Virol 65: 4547–4549
Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T, Kinasha KI, Shirakawa S, Miyoshi I (1981) Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci USA 78: 6476–6480
Hirai H, Fujisawa J, Suzuki T, Ueda K, Muramatsu M, Txuboi A, Arai N, Yoshida M (1992) Transcriptional activator Tax of HTLV-I binds to the NF-kappa B precursor p105. Oncogene 7: 1737–1742
Hjelle B, Appenzaller O, Mills R, Alexander S, Torrez, Martinez N, Jahuke R, Ross G (1992) Chronic neurodegenerative disease associated with HTLV-II infection. Lancet 339: 645–646
Howcroft TK, Strebel K, Martin MA, Singer DS (1993) Repression of MHC class-I gene promoter activity by two-exon Tat of HIV. Science 260: 1320–1322
Hoyos B, Ballard DW, Bohnlein E, Siekevitz M, Greene WC (1989) Kappa B-specific DNA binding proteins: role in the regulation of human IL-2 gene expression. Science 244: 457–460
Ikeda K, Weir EC, Mangin M, Dannies PS, Kinder B, Deftos KJ, Briwn EM, Broadus AE (1988) Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human parathyroid adenomas. Mol Endocrinol 2: 1230–1236
Ijichi S, Ramundo MB, Takahashi H, Hall WW (1992) In vivo cellular tropism of human T-cell leukemia virus type II (HTLV-II). J Exp Med 176: 293–296
Inoue J, Yoshida M, Seiki M (1987) Transcriptionai (p40X) and post-transcriptional (p27X-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci 84: 3653–3657
Ishibashi K, Ishitsuka K, Chuman Y, Otsuka M, Kuwazuru Y, Iwahashi M, Utsunomiya A, Hanada S, Sakurami T, Arima T (1991) Tumor necrosis factor-β in the serum of adult T-cell leukemia with hypercalcemia. Blood 77: 2451–2455
Jakobovits A, Rosenthal A, Capon DJ (1990) Trans-activation of HIV-1 LTR-directed gene expression by Tat requires protein kinase C. EMBO J 9: 1165–1170
Jacobson S, Zaninovic V, Mora C, Rodgers-Johnson P, Sheremata WA, Gibbs CJ, Gadjusek C, McFarlin DE (1988) Immunological findings in neurological diseases associated with antibodies to HTLV-I: activated lymphocytes in tropical spastic paraparesis. Ann Neurol 23: 5196–5200
Jacobson S, Shida H, McFarlin DE, Fauce AS, Keonig S (1990) Circulating CD8+ cytotoxic T-lymphocytes specific for HTLV-I pX in patients with HTLV-I-associated neurological disease. Nature 348: 245–248
Jeang KT, Widen SG, Semmes OJ IV, Wilson SH (1990) HTLV-I trans-activator protein, Tax, is a trans-repressor of the human beta-polymerase gene. Science 247: 1082–1084
Jocher R, Rethwilm A, Kappos L, Ter Meulen V (1990) Search for retroviral sequences in peripheral blood mononuclear cells and brain tissue of multiple sclerosis patients. J Neurol 237: 352–355
Kalyanaraman VS, Samgadharan MG, Robert-Gurrof M, Miyoshi I, Blayney D, Golde D, Gallo RC (1982) A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 218: 571
Kashiwamura SI, Garcia V, Agy M, Gale M, Katze M, Ledbetter JA, Clark EA (1990) Downregulation of CD28 expression by Tat protein from HIV-1. Symp Nonhum Primate Models AIDS 8: 136
Kanamori H, Suzuki N, Siomi H, Nosaka T, Sato A, Sabe H, Hatanaka M, Honjo T (1990) HTLV-I p27 Rex stabilizes human interleukin-2 receptor alpha chain mRNA. EMBO J 9: 4161–4166
Kato H, Sumimoto H, Pognonec P, Chen C-H, Rosen CA, Roeder RG (1992) HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev 6: 655–666.
Katoh T, Harada T, Morikawa S, Wakutani T(1986) IL-2 and IL-2R-independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients. Int J Cancer 38: 265–274
Kekow J, Wachsman W, McCutchan JA, Gross WL, Zachariah M, Carson DA, Lotz M (1991) Transforming growth factor and suppression of humoral immune responses in HIV infection. J Clin Invest 87: 1010–1016
Kelly K, Davis P, Mitsuya H, Irving S , Wright J, Grassman R, Fleckenstein B, Wano Y, Greene W, Siebenlist U (1992) A high proportion of early response genes are constitutively activated in T-cell by HTLV-I 7: 1463–1470
Kermer R, Karaplis AC, Henderson J, Gullver W, Banville D, Hendy GN, Goltzman D (1991) Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. J Clin Invest 87: 884–893
Kessler M, Mathews MB (1991) Tat transactivation of the human immunodeficiency virus type 1 promoter is influenced by basal promoter activity and the simian virus 40 origin of DNA replication. Proc Natl Acad Sci USA 88: 10018–10022
Kim SJ, Kehrl JH, Burton J, Tendier CL, Jean KT, Danielpour D, Thevenin C, Kim KY, Sporn MB, Roberts ANB (1990) Transactivation of the transforming growth factor β1 (TGF-β1) gene by human T-lymphotropic virus type 1 Tax: a potential mechanism for the increased production of TGF-β1 in adult T-cell leukemia. J Exp Med 172: 121
Kim YS, Risser R (1993) TAR-independent transactivation of the murine cytomegalovirus major immediate-early promoter by the Tat protein. J Virol 67: 239–248
Kitado H, Chen ISY, Shah NP, Cann AJ, Shimotohno K, Fan H (1987) U3 sequences from HTLV-I and -II LTRs confer px protein response to a murine leukemia virus LTR. Science 235: 901–904
Kitajima I, Shinohara T, Minor T, Bibbs L, Bilakovics J, Nerenberg M (1992) Human T-cell leukemia virus type I Tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo. J Biol Chem 267: 25881–25888
Kiyokawa T, Seiki M, Iwashita S (1985) p27X-III, and p21X-III, proteins encoded by the pX sequence of human T-cell leukemia virus type I. Proc Natl Acad Sci USA 82: 8359–8363
Koenig S, Woods RM, Brewah YA, Newell AJ, Jones GM, Boone E, Adelsberger JW, Baseler MW, Robinson SM, Jacobson S (1993) Characterization of MHC-I-restricted cytotoxic T-cell responses to Tax in HTLV-I infected patients with neurologic disease. J Immunol 151: 3874–3883
Laspia MF, Rice AP, Mathews MB (1989) HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell 59: 283–292
Lee TH, Coligan JE, Sodroski JG (1984) Antigens encoded by the 3′-terminal region of human T-cell leukemia virus: evidence for a functional gene. Science 226: 57–61
Leung K, Nabel G (1988) HTLV-I transactivator induces IL-2 receptor expression through an NFκB-like factor. Nature 333: 776
Lilienbaum A, Due Dodon M, Alexandre C, Gazzolo L, Paulin D (1990) Effect of human T-cell leukemia virus type I Tax protein on activation of the human vimentin gene. J Virol 64: 256–263
Lillehoj EP, Alexander SS Jr (1992) Virion-associated trans-regulatory protein of human T-cell leukemia virus type I. AIDS Res Hum Retroviruses 8: 237–244
Lindholm PF, Reid RL, Brady JN (1992) Extracellular Tax1 protein stimulates tumor necrosis factor-beta and immunoglobulin kappa light chain expression in lymphoid cells. J Virol 66: 1294–1302
Mace K, Seif I, Anjard C, De Maeyer-Guignard J, Dodon MD, Gazzolo L, De Maeyer E (1991) Enhanced resistance to HIV-1 replication in U937 cells stably transfected with the human IFN-γ gene behind an MHC promoter fragment. J Immunol 147: 3553–3559
Mangin M, Ikeda K, Dreyer BE, Broadus AE (1990) Identification of an upstream promoter of the human parathyroid hormone-related peptide gene. Mol Endocrinol 4: 851–858
Marciniak RA, Sharp PA (1991) HIV-1 Tat protein promotes formation of more processive elongation complexes. EMBO J 10: 4189–4196
Marciniak RA, Calnan BJ, Frankel AD, Sharp PA (1990) HIV-1 Tat protein trans-activates transcription in vitro. Cell 63: 791–802
Marriott SJ, Lindholm PF, Brown KM, Gitlin SD, Radonovich MF, Brady JN (1990) A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type 1 Tax with a responsive elements in the viral long terminal repeat. Mol Cell Biol 36: 4192
McGuire KL, Curtis VE, Larson EL, Haseltine WA (1993) Influence of human T-cell leukemia virus type I Tax and Rex on interleukin-2 gene expression. J Virol 67: 1590–1599
Merendino JJ, Insogna KL, Milstone LM, Boradus AE, Stewart AF (1986) A parathyroid hormone-like protein from cultured human keratinocytes. Science 231: 388–390
Miles S, Rezai A, Gaynor R, Magpantay L, Kishimoto T, Martinez-Maza O (1991) HIV-Tat increases IL-6 production by and proliferation of AIDS-KS-derived cells. Int Conf AIDS 7: 55
Miles SA, Rezai AR, Logan D, Salazar-Gonzalez JF, Vander Meyden M, Mitsuyasu RT, Taga T, Hirano T, Kishimoto T, Martinez-Maza O (1990) AIDS Kaposi’s sarcoma-derived cells produce and respond to interleukin 6. Int Conf AIDS 6: 112
Miles SA, Martinez-Maza O, Rezai A, Magpantay L, Kishimoto T, Nakamura S, Radka SF, Linsley S (1992) Oncostatin M as a potent mitogen for AIDS-Kaposi’s sarcoma-derived cells. Science 255: 1432–1434
Miura S, Ohtani K, Numata N, Niki M, Ohbo K, Ina Y, Gojobori T, Tanaka Y, Tozawa H, Nakamura M (1991) Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40Tax. Mol Cell Biol 11: 1313–1325
Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y, Shiraishi Y, Nageta K, Hinuma Y (1981) Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T-cells. Nature 294: 770–771
Moch H, Lang D, Stamminger T (1992) Strong trans-activation of the human cytomegalovirus major immediate-early enhancer by p40Tax of human T-cell leukemia virus type I via two repetitive Tax-responsive sequence elements. J Virol 66: 7346–7354
Motokura T, Fukumoto S, Matsumoto T, Takahashi S, Fujita A, Yamashita TR, Igarashi T, Ogata E (1989) Parathyroid hormone-related protein in adult T-cell leukemia-lymphoma. Ann Intern Med 111: 484
Muchardt C, Seeler JS, Gaynor RB (1992a) Regulation of HTLV-I gene expression by Tax and AP-2. New Biologist 4: 541–550
Muchardt C, Seeler JS, Nirula A, Gong S, Gaynor R (1992b) Transcription factor AP-2 activates gene expression of HTLV-I. EMBO J 11: 2573–2581
Muiler WE, Rytik PG, Okamoto T, Pfeifer K, Merz H, Schröder HC (1991) Increase of prion gene expression caused by the HIV-1 transactivator protein Tat in human astrocytes. Int Conf AIDS 7: 73
Myers G, Pavlakis GN (1991) Evolutionary potential of complex retroviruses. In: Wagner RR, Frankel-Conrat H (eds) Viruses: the retroviridae vol I. Plenum, New York
Nabel G, Baltimore D (1987) An inducible transcription factor activates expression of human immunodeficiency virus in T-cells. Nature 326: 711
Nagashima K, Yoshida M, Seiki M (1986) A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40X and two other phosphoproteins. J Virol 60: 394–399
Nakamura S, Salahuddin SZ, Biberfeld P, Ensoli B, Markham PD, Wong-Staal F, Gallo RC (1988) Kaposi’s sarcoma cells: long-term culture with growth factor from retrovirus-infected CD4+ T cells. Science 242: 426–430
Nelbock P, Dillon PJ, Perkins A, Rosen CA (1990) A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator. Science 248: 1650–1653
Nimer S (1991) Tax responsiveness of the GM-CSF promoter is mediated by mitogen-inducible sequences other than kappa B. New Biologist 3: 997–1004
Nimer SD, Gasson JC, Hu K, Smalberg I, Williams JL, Chen ISY, Rosenblatt JD (1989) Activation of the GM-CSF promoter by HTLV-I and II proteins. Oncogene 4: 671
Nosaka T, Siomi H, Adachi Y, Ishibashi M, Kubota S, Maki M, Hatanaka M (1989) Nucleolar targeting of human T-cell leukemia virus type I Rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA. Proc Natl Acad Sci USA 86: 9798–9802
Nyborg JK, Dynan WS, Chen ISY, Wachsman W (1988) Binding of host cell factors to DNA sequences in the long terminal repeat of human T-cell leukemia virus type I: implications for viral gene expression. Proc Natl Acad Sci USA 85: 1457–1461
Nyborg JK, Matthews MA, Yucel J, Walls L, Golde WT, Dynan WS, Wachsman W (1990) Interaction of host cell proteins with the human T-cell leukemia virus type I transcriptional control region. II. A comprehensive map of protein-binding sites facilitates construction of a simple chimeric promoter responsive to the viral Tax 2 gene product. J Biol Chem 265: 8237–8242
Ohtani K, Nakamura M, Saito S, Noda T, Ito Y, Sugamura K, Hinuma Y (1987) identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression. EMBO J 6: 389–395
Philippon V, Vellutini C, Metzger D, Gambarelli D, Vigne R, Harkiss GD, Hayman M, Arbuthnott G, Filippi P (1992) Evidence for neurotoxic activity of Tat peptides from visna virus and HIV in the mouse. Int Conf AIDS 8: A27
Pocsik E, Higuchi M, Aggarwal BB (1992) Down-modulation of cell surface expression of p80 form of the tumor necrosis factor receptor by human immunodeficiency virus-1 Tat gene. Lymphokine Cytokine Res 11: 317–325
Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) Detection and isolation of type C retrovirus particles from fresh and cultural lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci USA 77: 7415–7419
Poiesz BJ, Ruscetti FN, Reitz MS, Kalyanaraman VS, Gallo RC (1981) Isolation of a new type c retrovirus (HTLV) in primary uncultured cells of a patient with Sezary T- cell leukaemia. Nature 294: 268–271
Popovic M, Lange-Wantzin G, Sarin PS, Mann D, Gallo RC (1983) Transformation of human umbilical cord blood T-cells by human T-cell leukemia/lymphoma virus. Proc Natl Acad Sci USA 80: 5402–5406
Purvis SF, Georges DL, Williams TM, Lederman MM (1992) Suppression of interleukin-2 and interleukin-2 receptor expression in Jurket cells stably expressing the human immunodeficiency virus Tat protein. Cell Immunol 144: 32–42
Radonovich M, Jeang KT (1989) Activation of the human T-cell leukemia virus type I long terminal repeat by 12-0-tetradecanoylphorbol-13-acetate and by Tax (p40x) occurs through similar but functionally distinct target sequences. J Virol 63: 2987–2984
Rimsky L, Hauber J, Dukovich M, Malim MH, Langlois A, Cullen BR, Greene WC (1988) Functional replacement of the HIV-1 Rev protein by the HTLV-I Rex protein. Nature 335: 738–740
Robert-Guroff M, Popovic M, Gartner S, Markham P, Gallo RC, Reitz MS (1990) Structure and expression of Tat-, rev-, and nef-specific transcripts of human immunodeficiency virus type 1 in infected lymphocytes and macrophages. J Virol 64: 3391–3398.
Rosen CA, Sodroski JG, Haseltine WA (1985) Location of c/s-acting regulatory sequences in the human T-cell leukemia virus type I long terminal repeat. Proc Natl Acad Sci USA 82:6502–6506.
Rosenblatt JD, Golde DW, Wachsman W, Giorgi JV, Jacobs A, Schmidt GM, Quan S, Gasson JC, Chen ISY (1986) A second isolate of HTLV-II associated with atypical harry cell leukemia. NEJM 315: 372-377
Rosenblatt JD, Cann AJ, Slamon DJ, Smalberg IS, Shah NP, Fujii J, Wachsman W, Chen ISY (1988) HTLV-II transactivation is regulated by the overlapping Tax/Rex nonstructural genes. Science 240: 916–919
Rosenblatt JD, Plaeger Marshall S, George JV, Swanson P, Chen ISY, Chin E, Wong HJ, Canavaggio M, Hausner MA, Black AC (1990) A clinical, hematologic and immunologic analysis of 21 HTLV-II-infected intravenous drug users. Blood 76: 409–417
Rosenblatt JD, Tomkins P, Rosenthal M, Kacena A, Chen G, Valderama R, Harrington W Jr, Saxton E, Dragne A, Zhao JQ, Chen ISY, Weisbart R (1992) Progressive spastic myelopathy in a patient coinfected with HIV-1 and HTLV-II: autoantibodies to the human homologue of rig in blood and cerebrospinal fluid. AIDS 6: 1151–1158
Ruben SM, Rosen CA (1990) Suppression of signals required for activation of transcription factor NF-kappa B in cells constitutively expressing the HTLV-I Tax protein. New Biologist 2: 894–902
Ruben SM, Perkins A, Rosen CA (1989) Activation of NF-kappa B by the HTLV-I trans-activator protein Tax requires an additional factor present in lymphoid cells. New Biologist 1: 275–284
Ruben SM, Narayanan R, Klement JF, Chen CH, Rosen CA (1992) Functional characterization of the NFκB p65 transcriptional activator and an alternatively spliced derivative. Mol Cell Biol 12: 444–454
Sabatier JM, Vives E, Mabrouk K, Benjouad A, Rochat H, Duval A, Hue B, Bahraoui E (1991) Evidence for neurotoxic activity of Tat from human immunodeficiency virus type 1. J Virol 65: 961–967
Sagata N, Yasunaga T, Ikawa Y (1985) Two distinct polypeptides may be translated from a single spliced mRNA of the X genes of human T-cell leukemia and bovine leukemia viruses. FEBS Lett 192: 37–42
Sakamoto KM, Nimer SD, Rosenblatt JD, Gasson JC (1992) HTLV-I and HTLV-II Tax trans-activate the human EGR-1 promoter through different c/s-acting sequences. Oncogene 7: 2125–2130
Schwartz S, Felber BK, Benko DM, Fenyo E, Pavlakis GN (1990) Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type I. J Virol 64: 2519
Seiki M, Hattori S, Hirayama Y, Yoshida M (1993) Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci USA 80: 3618–3622
Seiki M, Eddy R, Shows TB, Yoshida M (1984) Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells. Nature 309: 640–642
Seiki M, Inoue J, Takeda T, Yoshida M (1986) Direct evidence that p40X of human T-cell leukemia virus type I is a transacting transcriptional activator. EMBO J 5: 561–565
Seth P, Wasson DB, Carson DA, Lotz M (1991) HIV Tat inhibits IFNγ-induced macrophage activation and antiviral activity. Int Conf AIDS 7: 164
Shibuya H, Irie K, Ninomiya-Tsuji J, Goebl M, Taniguchi T, Matsumoto K (1992) New human gene encoding a positive modulator of HIV-Tat-mediated transactivation. Nature 357: 700–702
Shima H, Takano M , Shimotohno K, Miwa M (1986) Identification of p26Xb and p24Xb of human T-cell leukemia virus type II. FEBS Lett 209: 289–294
Shimotohno K, Golde DW, Miwa M, Fugimura T, Chen ISY (1984) Nucleotide sequence analysis of the long terminal repeat of human T-cell leukemia virus type II. Proc Natl Acad Sci USA 81: 1079–1083
Shimotohno K, Takahashi Y, Shimuzu N, Gojobori T, Golde DW, Chen ISY, Miwa M, Sugimura T (1985) Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II. a new open reading frame for the protease gene. Proc Natl Acad Sci USA 82: 3101–3105
Shimotohno K, Takano M, Teruchi T, Miwa M (1986) Requirement of multiple copies of a 21-nucleotide sequence in the U3 regions of human T-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription. Proc Natl Acad Sci USA 83: 8112–8116
Shinohara T (1991) HTLV-I Tax mediated activation of cellular genes in transgenic mice. Hokkaido Igaku Xasshi. Hokkaido J Med Sci 66: 534–543
Siekevitz M, Feinberg MB, Holbrook N, Wong-staal F, Leonard WI (1987) Activation of interleukin-2 and interleukin-2 receptor (Tac) promoter expression by the trans-activator (Tat) gene product of human T-cell leukemia virus, type I. Proc Natl Acad Sci USA 84: 5389–5393
Slamon DJ, Shimotohno K, Cline MJ, Golde DW, Chen ISY (1984) Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science 226: 61–65
Slamon DJ, Press MF, Souza LM, Murdock DC, Cline MJ, Golde DW, Gasson JC, Chen ISY (1985) Studies of the putative transforming protein of the type I human T-cell leukemia virus. Science 228: 1427–1430
Smith MR, Greene WC (1990) Identification of HTLV-I Tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev 4: 1875–1885
Smith MR, Greene WC (1991) Type I human T-cell leukemia virus Tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. J Clin Invest 88: 1038–1042
Sodroski J, Rosen C, Goh WC, Haseitine W (1985) A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus. Science 228: 1430–1434
Southgate CD, Green MR (1991) The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function. Genes Dev 5: 2496–2507
Stein B, Cogswell PC, Baldwing AS Jr (1993) Functional and physical associations between NFκB and c/EBP family members: a rel domain-bZIP interaction. Mol Cell Biol 13: 3964–3974
Sukhatme VP, Cox X, Chang LC, Tsai-Morris C (1988) A zinc finger encoding gene co-regulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 53: 37–43
Sun SC, Ganchi PA, Ballard DW, Greene WC (1993) NFκB controls expression of inhibitor IκBa: evidence for an inducible autoregulatory pathway. Science 259: 1912–1915
Suva LJ, Winslow GA, Wettenhall REH, Hammonds RG, Moseley JM, Diefenback-Jagger H, Rodda CP, Kemp BE, Rodriguez H, Chen EY, Hudson PJ, Martin TJ, Wood WI (1987) A parathyroid hormonerelated protein implicated in malignant hypercalcemia cloning and expression. Science 237: 893–896
Tanaka A, Takahashi C, Yamaoka S, Nosaka T, Maki M, Hatanaka M (1990) Oncogenic transformation by the Tax gene of human T-cell leukemia virus type I in vitro. Proc Natl Acad Sci USA 87: 1071–1075
Taylor JP, Cupp C, Diaz A, Chowdhury M, Khalili K, Jimenez SA, Amini S (1992a) Activation of expression of genes coding for extracellular matrix proteins in Tat-producing glioblastoma cells. Proc Natl Acad Sci USA 89: 9617–9621
Taylor JP, Pomerantz R, Bagasra O, Chowdhury M, Rappaport J, Khalili K, Amini S (1992b) TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J 11: 3395–3403
Tendier CL, Greenberg SJ, Blattner WA, Manns A, Murphy E, Fleisher T, Hanchard B, Morgan O, Burton JD, Nelson DL, Waldmann TA (1990) Transactivation of interleukin 2 and its receptor induces immune activation in HTLV-1 associated myelopathy; pathogenic implications and a rationale for immunotherapy. Proc Natl Acad Sci USA 87: 5218–5222
Thiede MA, Rodan GA (1988) Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Science 24: 278–280
Thiede MA, Daifotis AG, Weir EC, Brines ML, Burtis WJ, Ikeda K, Dreyer BE, Garfield RE, Broadus AE. (1990) Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium. Proc Natl Acad Sci USA 87: 6969–6973
Tsujimoto A, Nyunoya H, Morita T, Sato T, Shimotohno K (1991) Isolation of cDNAs for DNA-binding proteins which specifically bind to a Tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I. J Virol 65: 1420–1426
Vernon SD, Hart CE, Reeves WC, Icenogle JP (1993) The HIV-1 Tat protein enhances E2-dependent human papillomavirus 16 transcription. Virus Res 27: 133–145
Vogel BE, Lee SJ, Hildebrand A, Craig W, Pierschbacher MD, Wong-staal F, Ruoslahti E (1993) A novel integrin specificity exemplified by binding of the v5integrin to the basic domain of the HIV Tat protein and vitronectin. J Cell Biol 121: 461–468
Vogel J, Hinrichs SH, Reynolds RK, Luciw PA, Jay G (1988) The HIV Tat gene induces dermal lesions resembling Kaposi’s sarcoma in transgenic mice. Nature 335: 606–611
Wagner S, Green MR (1993) HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. Science 262: 395–399
Wano Y, Feinberg M, Hosking JB, Bogerd H, Greene WC (1988). Stable expression of the Tax gene of type human T-cell leukemia virus in human T-cells activates specific cellular genes involved in growth. Proc Natl acad Sci USA 85: 9733`–9737
Watanabe T, Yamaguchi K, Takasuki K, Osame M, Yoshida M (1990) Constitutive expression of parathyroid hormone-related protein gene in human T-cell leukemia virus type 1 (HTLV-1) carriers and adult T-cell leukemia patients that can be transactivated by HTLV-1 Tax gene. J Exp Med 172: 759–765
Weeks BS, Klotman ME, Dhawan S, Kibbey M, Rappaport J, Kleinman HK, Yamada KM, Klotman PE (1991) HIV-1 infection of human T lymphocytes results in enhanced integrin expression. J Cell Biol 114: 847–853
Weeks BS, Desai K, Loewenstein PM, Klotman ME, Klotman PE, Green M, Kleinman HK (1993) Identification of a novel cell attachment domain in the HIV-1 Tat protein and its 90-kDa cell surface binding protein. J Biol Chem 268: 5279–5284
Weich HA, Zaki Salahuddin S, Gill P, Nakamura S, Gallo RC, Folkmann J (1991) AIDS-associated Kaposi’s sarcoma-derived cells in long-term culture express and synthesize smooth muscle alpha-actin. Am J Pathol 139: 1251–1258
Weir EC, Brines ML, Ikeda K, Burtis WJ, Broadus AE, Robins RJ (1990) Parathyroid hormone-related peptide gene is expressed in the mammalian central nervous system. Proc Natl Acad Sci USA 87: 108–112
Wright JJ, Gunter KC, Mitsuya H, Irving SG, Kellyy K, Siebenlist U (1990) Expression of a zinc finger gene in HTLV-I and HTLV-II transformed cells. Science 248: 588
Xu YL, Adya N, Siores E, Gao QS, Giam CZ (1990) Cellular factors involved in transcription and Tax-mediated trans-activation directed by the TGACGT motifs in human T-cell leukemia virus type I promoter. J Biol Chem 265: 20285–20292
Yamamoto N, Okada M, Koyanagi Y, Kannagi M, Hinuma Y (1982) Transformation of human leukocytes by cocultivation with an adult T-cell leukemia virus producer cell line. Science 217: 737–739
Yamaoka S, Tobe T, Hatanaka M (1992) Tax protein of human T-cell leukemia virus type I is required for maintenance of the transformed phenotype. Oncogene 7: 433–437
Yip MT, Chen IS (1990) Modes of transformation by the human T-cell leukemia viruses. Mol Biol Med 7: 33–44
Yip MT, Dynan WS, Green PL, Black AC, Arrigo SJ, Torbati A, Heaphy S, Ruland CT, Rosenblatt JD, Chen ISY (1991) Human T-cell leukemia virus (HTLV) type II Rex protein binds specifically to RNA sequences of the HTLV long terminal repeat but poorly to the human immunodeficiency virus type I Rev-reponsive element. J Virol 65: 2261–2272
Yoshida M, Miyoshi I, Hinuma Y (1982) Isolation and characterization of retrovirus from cell line of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci USA 79: 2031–2035
Yoshida M, Osame M, Usuku K et al (1987) Viruses detected in HTLV-I associated myelopathy and adult T-cell leukaemia are identical on DNA blotting. Lancet 1: 1085–1086
Yoshida M, Inoue J, Fujisawa J, Seiki M (1989) Molecular mechanisms of regulation of HTLV-I gene expression and its association with leukemogenesis. Genome 31: 662–667
Yoshimura T, Fujisawa J, Yoshida M (1990) Multiple cDNA clones encoding nuclear proteins that bind to the Tax-dependent enhancer of HTLV-I: all contain a leucine zipper structure and basic amino acid domain. EMBO J 9: 2537–2542
Zauli G, Davis BR, Re MC, Visani G, Furlini G, La Placa M (1992) Tat protein stimulates production of transforming growth factor-beta 1 by marrow macrophages: a potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression. Blood 80: 3036–3043
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Rosenblatt, J.D., Miles, S., Gasson, J.C., Prager, D. (1995). Transactivation of Cellular Genes by Human Retroviruses. In: Chen, I.S.Y., Koprowski, H., Srinivasan, A., Vogt, P.K. (eds) Transacting Functions of Human Retroviruses. Current Topics in Microbiology and Immunology, vol 193. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78929-8_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-78929-8_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-78931-1
Online ISBN: 978-3-642-78929-8
eBook Packages: Springer Book Archive