Biopolym. Cell. 1994; 10(5):5-30.
HIV-1 regulatory genes and their role in the viral genome realization
1Kukharenko A. P., 1Shved A. D.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


Review summarises recent data related to the role and function of the auxiliary regulatory genes nef, vpu, vpr, vif, tat and rev of HIV-1 in viral replication. We devoted attention rather to the tat, rev, nef and their products as to the main regulators of the realization of HIV-1 lentiviral genome. Possible mechanisms of influence of these viral products on proviral activity in couple with host-cellular factors are considered. Cytopathophysiological effections of some viral regulatory proteins upon HIV-1 persistention of permissible cells are also shortly reviewed.


[1] Delassus S, Cheynier R, Wain-Hobson S. Evolution of human immunodeficiency virus type 1 nef and long terminal repeat sequences over 4 years in vivo and in vitro. J Virol. 1991;65(1):225-31.
[2] Kaminchik J, Bashan N, Itach A, Sarver N, Gorecki M, Panet A. Genetic characterization of human immunodeficiency virus type 1 nef gene products translated in vitro and expressed in mammalian cells. J Virol. 1991;65(2):583-8.
[3] Guy B, Rivière Y, Dott K, Regnault A, Kieny MP. Mutational analysis of the HIV nef protein. Virology. 1990;176(2):413-25.
[4] Michael NL, Morrow P, Mosca J, Vahey M, Burke DS, Redfield RR. Induction of human immunodeficiency virus type 1 expression in chronically infected cells is associated primarily with a shift in RNA splicing patterns. J Virol. 1991;65(3):1291-303.
[5] Laurent AG, Hovanessian AG, Rivière Y, Krust B, Regnault A, Montagnier L, Findeli A, Kieny MP, Guy B. Production of a non-functional nef protein in human immunodeficiency virus type 1-infected CEM cells. J Gen Virol. 1990;71 ( Pt 10):2273-81.
[6] Cullen BR, Greene WC. Functions of the auxiliary gene products of the human immunodeficiency virus type 1. Virology. 1990;178(1):1-5.
[7] Nebreda AR, Bryan T, Segade F, Wingfield P, Venkatesan S, Santos E. Biochemical and biological comparison of HIV-1 NEF and ras gene products. Virology. 1991;183(1):151-9.
[8] Kim S, Ikeuchi K, Byrn R, Groopman J, Baltimore D. Lack of a negative influence on viral growth by the nef gene of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989;86(23):9544-8.
[9] Hammes SR, Dixon EP, Malim MH, Cullen BR, Greene WC. Nef protein of human immunodeficiency virus type 1: evidence against its role as a transcriptional inhibitor. Proc Natl Acad Sci U S A. 1989;86(23):9549-53.
[10] Bachelerie F, Alcami J, Hazan U, Israël N, Goud B, Arenzana-Seisdedos F, Virelizier JL. Constitutive expression of human immunodeficiency virus (HIV) nef protein in human astrocytes does not influence basal or induced HIV long terminal repeat activity. J Virol. 1990;64(6):3059-62.
[11] de Ronde A, Klaver B, Keulen W, Smit L, Goudsmit J. Natural HIV-1 NEF accelerates virus replication in primary human lymphocytes. Virology. 1992;188(1):391-5.
[12] Skowronski J, Parks D, Mariani R. Altered T cell activation and development in transgenic mice expressing the HIV-1 nef gene. EMBO J. 1993;12(2):703-13.
[13] Ahmad N, Venkatesan S. Nef protein of HIV-1 is a transcriptional repressor of HIV-1 LTR. Science. 1988;241(4872):1481-5. Erratum in: Science 1988 Oct 7;242(4875):242.
[14] Cheng-Mayer C, Iannello P, Shaw K, Luciw PA, Levy JA. Differential effects of nef on HIV replication: implications for viral pathogenesis in the host. Science. 1989;246(4937):1629-32.
[15] Luria S, Chambers I, Berg P. Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. Proc Natl Acad Sci U S A. 1991;88(12):5326-30.
[16] Poulin L, Levy JA. The HIV-1 nef gene product is associated with phosphorylation of a 46 kD cellular protein. AIDS. 1992;6(8):787-91.
[17] Werner T, Ferroni S, Saermark T, Brack-Werner R, Banati RB, Mager R, Steinaa L, Kreutzberg GW, Erfle V. HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels. AIDS. 1991;5(11):1301-8.
[18] Burch HB, Nagy EV, Lukes YG, Cai WY, Wartofsky L, Burman KD. Nucleotide and amino acid homology between the human thyrotropin receptor and the HIV-1 Nef protein: identification and functional analysis. Biochem Biophys Res Commun. 1991;181(1):498-505.
[19] Strebel K, Klimkait T, Maldarelli F, Martin MA. Molecular and biochemical analyses of human immunodeficiency virus type 1 vpu protein. J Virol. 1989;63(9):3784-91.
[20] Strebel K, Klimkait T, Martin MA. A novel gene of HIV-1, vpu, and its 16-kilodalton product. Science. 1988;241(4870):1221-3.
[21] Terwilliger EF, Cohen EA, Lu YC, Sodroski JG, Haseltine WA. Functional role of human immunodeficiency virus type 1 vpu. Proc Natl Acad Sci U S A. 1989;86(13):5163-7.
[22] Arrigo SJ, Chen IS. Rev is necessary for translation but not cytoplasmic accumulation of HIV-1 vif, vpr, and env/vpu 2 RNAs. Genes Dev. 1991;5(5):808-19.
[23] Schwartz S, Felber BK, Fenyö EM, Pavlakis GN. Env and Vpu proteins of human immunodeficiency virus type 1 are produced from multiple bicistronic mRNAs. J Virol. 1990;64(11):5448-56.
[24] Cohen EA, Dehni G, Sodroski JG, Haseltine WA. Human immunodeficiency virus vpr product is a virion-associated regulatory protein. J Virol. 1990;64(6):3097-9.
[25] Shibata R, Miura T, Hayami M, Ogawa K, Sakai H, Kiyomasu T, Ishimoto A, Adachi A. Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) genome in relation to HIV-1 and simian immunodeficiency virus SIV (AGM). J Virol. 1990;64(2):742-7.
[26] Ogawa K, Shibata R, Kiyomasu T, Higuchi I, Kishida Y, Ishimoto A, Adachi A. Mutational analysis of the human immunodeficiency virus vpr open reading frame. J Virol. 1989;63(9):4110-4.
[27] Levy DN, Fernandes LS, Williams WV, Weiner DB. Induction of cell differentiation by human immunodeficiency virus 1 vpr. Cell. 1993;72(4):541-50.
[28] Sakai H, Shibata R, Miura T, Hayami M, Ogawa K, Kiyomasu T, Ishimoto A, Adachi A. Complementation of the rev gene mutation among human and simian lentiviruses. J Virol. 1990;64(5):2202-7.
[29] Golub EI, Li GG, Volsky DJ. Differences in the basal activity of the long terminal repeat determine different replicative capacities of two closely related human immunodeficiency virus type 1 isolates. J Virol. 1990;64(8):3654-60.
[30] Sakai K, Ma XY, Gordienko I, Volsky DJ. Recombinational analysis of a natural noncytopathic human immunodeficiency virus type 1 (HIV-1) isolate: role of the vif gene in HIV-1 infection kinetics and cytopathicity. J Virol. 1991;65(11):5765-73.
[31] Felber BK, Drysdale CM, Pavlakis GN. Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein. J Virol. 1990;64(8):3734-41.
[32] Terwilliger E, Burghoff R, Sia R, Sodroski J, Haseltine W, Rosen C. The art gene product of human immunodeficiency virus is required for replication. J Virol. 1988;62(2):655-8.
[33] Hammarskjöld ML, Heimer J, Hammarskjöld B, Sangwan I, Albert L, Rekosh D. Regulation of human immunodeficiency virus env expression by the rev gene product. J Virol. 1989;63(5):1959-66.
[34] Sodroski J, Goh WC, Rosen C, Dayton A, Terwilliger E, Haseltine W. A second post-transcriptional trans-activator gene required for HTLV-III replication. Nature. 1986 May 22-28;321(6068):412-7.
[35] Cochrane AW, Golub E, Volsky D, Ruben S, Rosen CA. Functional significance of phosphorylation to the human immunodeficiency virus Rev protein. J Virol. 1989;63(10):4438-40.
[36] Hope TJ, McDonald D, Huang XJ, Low J, Parslow TG. Mutational analysis of the human immunodeficiency virus type 1 Rev transactivator: essential residues near the amino terminus. J Virol. 1990;64(11):5360-6.
[37] Zapp ML, Green MR. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature. 1989;342(6250):714-6.
[38] Sadaie MR, Benter T, Wong-Staal F. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1. Science. 1988;239(4842):910-3.
[39] Cochrane AW, Perkins A, Rosen CA. Identification of sequences important in the nucleolar localization of human immunodeficiency virus Rev: relevance of nucleolar localization to function. J Virol. 1990;64(2):881-5.
[40] Kubota S, Nosaka T, Cullen BR, Maki M, Hatanaka M. Effects of chimeric mutants of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex on nucleolar targeting signals. J Virol. 1991;65(5):2452-6.
[41] Hadzopoulou-Cladaras M, Felber BK, Cladaras C, Athanassopoulos A, Tse A, Pavlakis GN. The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region. J Virol. 1989;63(3):1265-74.
[42] Malim MH, Böhnlein S, Hauber J, Cullen BR. Functional dissection of the HIV-1 Rev trans-activator--derivation of a trans-dominant repressor of Rev function. Cell. 1989;58(1):205-14.
[43] Rimsky L, Dodon MD, Dixon EP, Greene WC. Trans-dominant inactivation of HTLV-I and HIV-1 gene expression by mutation of the HTLV-I Rex transactivator. Nature. 1989;341(6241):453-6.
[44] Dillon PJ, Nelbock P, Perkins A, Rosen CA. Structural and functional analysis of the human immunodeficiency virus type 2 Rev protein. J Virol. 1991;65(1):445-9.
[45] Böhnlein S, Pirker FP, Hofer L, Zimmermann K, Bachmayer H, Böhnlein E, Hauber J. Transdominant repressors for human T-cell leukemia virus type I rex and human immunodeficiency virus type 1 rev function. J Virol. 1991;65(1):81-8.
[46] Daly TJ, Rennert P, Lynch P, Barry JK, Dundas M, Rusche JR, Doten RC, Auer M, Farrington GK. Perturbation of the carboxy terminus of HIV-1 Rev affects multimerization on the Rev responsive element. Biochemistry. 1993;32(34):8945-54.
[47] Malim MH, Cullen BR. HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency. Cell. 1991;65(2):241-8.
[48] Felber BK, Hadzopoulou-Cladaras M, Cladaras C, Copeland T, Pavlakis GN. rev protein of human immunodeficiency virus type 1 affects the stability and transport of the viral mRNA. Proc Natl Acad Sci U S A. 1989;86(5):1495-9.
[49] Knight DM, Flomerfelt FA, Ghrayeb J. Expression of the art/trs protein of HIV and study of its role in viral envelope synthesis. Science. 1987;236(4803):837-40.
[50] Emerman M, Vazeux R, Peden K. The rev gene product of the human immunodeficiency virus affects envelope-specific RNA localization. Cell. 1989;57(7):1155-65.
[51] Kim JH, Kaufman PA, Hanly SM, Rimsky LT, Greene WC. Rex transregulation of human T-cell leukemia virus type II gene expression. J Virol. 1991;65(1):405-14.
[52] Rosen CA, Terwilliger E, Dayton A, Sodroski JG, Haseltine WA. Intragenic cis-acting art gene-responsive sequences of the human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988;85(7):2071-5.
[53] Malim MH, Hauber J, Le SY, Maizel JV, Cullen BR. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989;338(6212):254-7.
[54] Dayton ET, Powell DM, Dayton AI. Functional analysis of CAR, the target sequence for the Rev protein of HIV-1. Science. 1989;246(4937):1625-9.
[55] Lewis N, Williams J, Rekosh D, Hammarskjöld ML. Identification of a cis-acting element in human immunodeficiency virus type 2 (HIV-2) that is responsive to the HIV-1 rev and human T-cell leukemia virus types I and II rex proteins. J Virol. 1990;64(4):1690-7.
[56] Yip MT, Dynan WS, Green PL, Black AC, Arrigo SJ, Torbati A, Heaphy S, Ruland C, Rosenblatt JD, Chen IS. 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 1 Rev-responsive element. J Virol. 1991;65(5):2261-72.
[57] Daly TJ, Cook KS, Gray GS, Maione TE, Rusche JR. Specific binding of HIV-1 recombinant Rev protein to the Rev-responsive element in vitro. Nature. 1989;342(6251):816-9.
[58] Huang XJ, Hope TJ, Bond BL, McDonald D, Grahl K, Parslow TG. Minimal Rev-response element for type 1 human immunodeficiency virus. J Virol. 1991;65(4):2131-4.
[59] Cook KS, Fisk GJ, Hauber J, Usman N, Daly TJ, Rusche JR. Characterization of HIV-1 REV protein: binding stoichiometry and minimal RNA substrate. Nucleic Acids Res. 1991;19(7):1577-83.
[60] Karn J, Dingwall C, Finch JT, Heaphy S, Gait MJ. RNA binding by the tat and rev proteins of HIV-1. Biochimie. 1991;73(1):9-16.
[61] Heaphy S, Finch JT, Gait MJ, Karn J, Singh M. Human immunodeficiency virus type 1 regulator of virion expression, rev, forms nucleoprotein filaments after binding to a purine-rich "bubble" located within the rev-responsive region of viral mRNAs. Proc Natl Acad Sci U S A. 1991;88(16):7366-70.
[62] Holland SM, Chavez M, Gerstberger S, Venkatesan S. A specific sequence with a bulged guanosine residue(s) in a stem-bulge-stem structure of Rev-responsive element RNA is required for trans activation by human immunodeficiency virus type 1 Rev. J Virol. 1992;66(6):3699-706.
[63] Iwai S, Pritchard C, Mann DA, Karn J, Gait MJ. Recognition of the high affinity binding site in rev-response element RNA by the human immunodeficiency virus type-1 rev protein. Nucleic Acids Res. 1992;20(24):6465-72.
[64] Lu YC, Touzjian N, Stenzel M, Dorfman T, Sodroski JG, Haseltine WA. Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1. J Virol. 1990;64(10):5226-9.
[65] Chang DD, Sharp PA. Regulation by HIV Rev depends upon recognition of splice sites. Cell. 1989;59(5):789-95.
[66] Chang DD, Sharp PA. Messenger RNA transport and HIV rev regulation. Science. 1990;249(4969):614-5.
[67] Kjems J, Brown M, Chang DD, Sharp PA. Structural analysis of the interaction between the human immunodeficiency virus Rev protein and the Rev response element. Proc Natl Acad Sci U S A. 1991;88(3):683-7.
[68] Olsen HS, Cochrane AW, Dillon PJ, Nalin CM, Rosen CA. Interaction of the human immunodeficiency virus type 1 Rev protein with a structured region in env mRNA is dependent on multimer formation mediated through a basic stretch of amino acids. Genes Dev. 1990;4(8):1357-64.
[69] Lu XB, Heimer J, Rekosh D, Hammarskjöld ML. U1 small nuclear RNA plays a direct role in the formation of a rev-regulated human immunodeficiency virus env mRNA that remains unspliced. Proc Natl Acad Sci U S A. 1990;87(19):7598-602.
[70] Fankhauser C, Izaurralde E, Adachi Y, Wingfield P, Laemmli UK. Specific complex of human immunodeficiency virus type 1 rev and nucleolar B23 proteins: dissociation by the Rev response element. Mol Cell Biol. 1991;11(5):2567-75.
[71] Constantoulakis P, Campbell M, Felber BK, Nasioulas G, Afonina E, Pavlakis GN. Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene. Science. 1993;259(5099):1314-8.
[72] Robert-Guroff M, Popovic M, Gartner S, Markham P, Gallo RC, Reitz MS. Structure and expression of tat-, rev-, and nef-specific transcripts of human immunodeficiency virus type 1 in infected lymphocytes and macrophages. J Virol. 1990;64(7):3391-8.
[73] Schwartz S, Felber BK, Benko DM, Fenyö EM, Pavlakis GN. Cloning and functional analysis of multiply spliced mRNA species of human immunodeficiency virus type 1. J Virol. 1990;64(6):2519-29.
[74] Berkhout B, Silverman RH, Jeang KT. Tat trans-activates the human immunodeficiency virus through a nascent RNA target. Cell. 1989;59(2):273-82.
[75] Wright CM, Felber BK, Paskalis H, Pavlakis GN. Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science. 1986;234(4779):988-92.
[76] Benko DM, Schwartz S, Pavlakis GN, Felber BK. A novel human immunodeficiency virus type 1 protein, tev, shares sequences with tat, env, and rev proteins. J Virol. 1990;64(6):2505-18.
[77] Sadaie MR, Mukhopadhyaya R, Benaissa ZN, Pavlakis GN, Wong-Staal F. Conservative mutations in the putative metal-binding region of human immunodeficiency virus tat disrupt virus replication. AIDS Res Hum Retroviruses. 1990;6(11):1257-63.
[78] Gitlin SD, Lindholm PF, Marriott SJ, Brady JN. Transdominant human T-cell lymphotropic virus type I TAX1 mutant that fails to localize to the nucleus. J Virol. 1991;65(5):2612-21.
[79] Green M, Ishino M, Loewenstein PM. Mutational analysis of HIV-1 Tat minimal domain peptides: identification of trans-dominant mutants that suppress HIV-LTR-driven gene expression. Cell. 1989;58(1):215-23.
[80] Carroll R, Martarano L, Derse D. Identification of lentivirus tat functional domains through generation of equine infectious anemia virus/human immunodeficiency virus type 1 tat gene chimeras. J Virol. 1991;65(7):3460-7.
[81] Feinberg MB, Jarrett RF, Aldovini A, Gallo RC, Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986;46(6):807-17.
[82] Feng S, Holland EC. HIV-1 tat trans-activation requires the loop sequence within tar. Nature. 1988;334(6178):165-7.
[83] Hauber J, Perkins A, Heimer EP, Cullen BR. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. Proc Natl Acad Sci U S A. 1987;84(18):6364-8.
[84] Jakobovits A, Smith DH, Jakobovits EB, Capon DJ. A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator. Mol Cell Biol. 1988;8(6):2555-61.
[85] Selby MJ, Bain ES, Luciw PA, Peterlin BM. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 1989;3(4):547-58.
[86] Selby MJ, Peterlin BM. Trans-activation by HIV-1 Tat via a heterologous RNA binding protein. Cell. 1990;62(4):769-76.
[87] Gatignol A, Buckler-White A, Berkhout B, Jeang KT. Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR. Science. 1991;251(5001):1597-600.
[88] Weeks KM, Ampe C, Schultz SC, Steitz TA, Crothers DM. Fragments of the HIV-1 Tat protein specifically bind TAR RNA. Science. 1990;249(4974):1281-5.
[89] Cordingley MG, LaFemina RL, Callahan PL, Condra JH, Sardana VV, Graham DJ, Nguyen TM, LeGrow K, Gotlib L, Schlabach AJ, et al. Sequence-specific interaction of Tat protein and Tat peptides with the transactivation-responsive sequence element of human immunodeficiency virus type 1 in vitro. Proc Natl Acad Sci U S A. 1990;87(22):8985-9.
[90] Roy S, Parkin NT, Rosen C, Itovitch J, Sonenberg N. Structural requirements for trans activation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by tat: importance of base pairing, loop sequence, and bulges in the tat-responsive sequence. J Virol. 1990;64(3):1402-6.
[91] Weeks KM, Crothers DM. RNA recognition by Tat-derived peptides: interaction in the major groove? Cell. 1991;66(3):577-88.
[92] Kao SY, Calman AF, Luciw PA, Peterlin BM. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product. Nature. 1987 Dec 3-9;330(6147):489-93.
[93] Rice AP, Mathews MB. Transcriptional but not translational regulation of HIV-1 by the tat gene product. Nature. 1988;332(6164):551-3.
[94] Feinberg MB, Baltimore D, Frankel AD. The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc Natl Acad Sci U S A. 1991;88(9):4045-9.
[95] Braddock M, Chambers A, Wilson W, Esnouf MP, Adams SE, Kingsman AJ, Kingsman SM. HIV-1 TAT "activates" presynthesized RNA in the nucleus. Cell. 1989;58(2):269-79.
[96] Braddock M, Thorburn AM, Chambers A, Elliott GD, Anderson GJ, Kingsman AJ, Kingsman SM. A nuclear translational block imposed by the HIV-1 U3 region is relieved by the Tat-TAR interaction. Cell. 1990;62(6):1123-33.
[97] Braddock M, Thorburn AM, Kingsman AJ, Kingsman SM. Blocking of Tat-dependent HIV-1 RNA modification by an inhibitor of RNA polymerase II processivity. Nature. 1991;350(6317):439-41.
[98] Chin DJ, Selby MJ, Peterlin BM. Human immunodeficiency virus type 1 Tat does not transactivate mature trans-acting responsive region RNA species in the nucleus or cytoplasm of primate cells. J Virol. 1991;65(4):1758-64.
[99] Laspia MF, Rice AP, Mathews MB. HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell. 1989;59(2):283-92.
[100] Cullen BR. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986;46(7):973-82.
[101] Greenblatt J, Nodwell JR, Mason SW. Transcriptional antitermination. Nature. 1993;364(6436):401-6.
[102] Gunnery S, Rice AP, Robertson HD, Mathews MB. Tat-responsive region RNA of human immunodeficiency virus 1 can prevent activation of the double-stranded-RNA-activated protein kinase. Proc Natl Acad Sci U S A. 1990;87(22):8687-91.
[103] Berkhout B, Gatignol A, Rabson AB, Jeang KT. TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. Cell. 1990;62(4):757-67.
[104] Southgate C, Zapp ML, Green MR. Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. Nature. 1990;345(6276):640-2.
[105] Selby MJ, Peterlin BM. Trans-activation by HIV-1 Tat via a heterologous RNA binding protein. Cell. 1990;62(4):769-76.
[106] Kamine J, Chinnadurai G. Synergistic activation of the human immunodeficiency virus type 1 promoter by the viral Tat protein and cellular transcription factor Sp1. J Virol. 1992;66(6):3932-6.
[107] Han XM, Laras A, Rounseville MP, Kumar A, Shank PR. Human immunodeficiency virus type 1 Tat-mediated trans activation correlates with the phosphorylation state of a cellular TAR RNA stem-binding factor. J Virol. 1992;66(7):4065-72.
[108] Wu F, Garcia J, Sigman D, Gaynor R. tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185. Genes Dev. 1991;5(11):2128-40.
[109] Ratnasabapathy R, Sheldon M, Johal L, Hernandez N. The HIV-1 long terminal repeat contains an unusual element that induces the synthesis of short RNAs from various mRNA and snRNA promoters. Genes Dev. 1990;4(12A):2061-74.
[110] Han P, Brown R, Barsoum J. Transactivation of heterologous promoters by HIV-1 tat. Nucleic Acids Res. 1991;19(25):7225-9.
[111] Berkhout B, Jeang KT. Functional roles for the TATA promoter and enhancers in basal and Tat-induced expression of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1992;66(1):139-49.
[112] Olsen HS, Rosen CA. Contribution of the TATA motif to Tat-mediated transcriptional activation of human immunodeficiency virus gene expression. J Virol. 1992;66(9):5594-7.
[113] Bachelerie F, Alcami J, Arenzana-Seisdedos F, Virelizier JL. HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes. Nature. 1991;350(6320):709-12.
[114] Sullenger BA, Gallardo HF, Ungers GE, Gilboa E. Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell. 1990;63(3):601-8.
[115] Graham GJ, Maio JJ. RNA transcripts of the human immunodeficiency virus transactivation response element can inhibit action of the viral transactivator. Proc Natl Acad Sci U S A. 1990;87(15):5817-21.
[116] Pfeifer K, Bachmann M, Schröder HC, Weiler BE, Ugarkovic D, Okamoto T, Müller WE. Formation of a small ribonucleoprotein particle between Tat protein and trans-acting response element in human immunodeficiency virus-infected cells. J Biol Chem. 1991;266(22):14620-6.
[117] Desai K, Loewenstein PM, Green M. Isolation of a cellular protein that binds to the human immunodeficiency virus Tat protein and can potentiate transactivation of the viral promoter. Proc Natl Acad Sci U S A. 1991;88(20):8875-9.
[118] Nelbock P, Dillon PJ, Perkins A, Rosen CA. A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator. Science. 1990;248(4963):1650-3.
[119] Shibuya H, Irie K, Ninomiya-Tsuji J, Goebl M, Taniguchi T, Matsumoto K. New human gene encoding a positive modulator of HIV Tat-mediated transactivation. Nature. 1992;357(6380):700-2.
[120] Kim YS, Risser R. TAR-independent transactivation of the murine cytomegalovirus major immediate-early promoter by the Tat protein. J Virol. 1993;67(1):239-48.
[121] Taylor JP, Pomerantz R, Bagasra O, Chowdhury M, Rappaport J, Khalili K, Amini S. TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation. EMBO J. 1992;11(9):3395-403.
[122] Remenick J, Radonovich MF, Brady JN. Human immunodeficiency virus Tat transactivation: induction of a tissue-specific enhancer in a nonpermissive cell line. J Virol. 1991;65(10):5641-6.
[123] Kato H, Sumimoto H, Pognonec P, Chen CH, Rosen CA, Roeder RG. HIV-1 Tat acts as a processivity factor in vitro in conjunction with cellular elongation factors. Genes Dev. 1992;6(4):655-66.
[124] Ensoli B, Barillari G, Salahuddin SZ, Gallo RC, Wong-Staal F. Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. Nature. 1990;345(6270):84-6.
[125] Zauli G, Furlini G, Re MC, Milani D, Capitani S, La Placa M. Human immunodeficiency virus type 1 (HIV-1) tat-protein stimulates the production of interleukin-6 (IL-6) by peripheral blood monocytes. New Microbiol. 1993;16(2):115-20.
[126] Sastry KJ, Reddy HR, Pandita R, Totpal K, Aggarwal BB. HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line. J Biol Chem. 1990;265(33):20091-3.
[127] Zauli G, Davis BR, Re MC, Visani G, Furlini G, La Placa M. 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. 1992;80(12):3036-43.
[128] Howcroft TK, Strebel K, Martin MA, Singer DS. Repression of MHC class I gene promoter activity by two-exon Tat of HIV. Science. 1993;260(5112):1320-2.
[129] Mann DA, Frankel AD. Endocytosis and targeting of exogenous HIV-1 Tat protein. EMBO J. 1991;10(7):1733-9.
[130] Helland DE, Welles JL, Caputo A, Haseltine WA. Transcellular transactivation by the human immunodeficiency virus type 1 tat protein. J Virol. 1991;65(8):4547-9.
[131] Cullen BR. Does HIV-1 Tat induce a change in viral initiation rights? Cell. 1993;73(3):417-20.
[132] Nicholas J, Nevins JR. Distinct DNA targets for trans-activation by HTLV-1 tax and adenovirus E1A. Virology. 1991;182(1):156-67.
[133] Seigel LJ, Ratner L, Josephs SF, Derse D, Feinberg MB, Reyes GR, O'Brien SJ, Wong-Staal F. Transactivation induced by human T-lymphotropic virus type III (HTLV III) maps to a viral sequence encoding 58 amino acids and lacks tissue specificity. Virology. 1986;148(1):226-31.
[134] Drysdale CM, Pavlakis GN. Rapid activation and subsequent down-regulation of the human immunodeficiency virus type 1 promoter in the presence of Tat: possible mechanisms contributing to latency. J Virol. 1991;65(6):3044-51.
[135] Wagner S, Green MR. HTLV-I Tax protein stimulation of DNA binding of bZIP proteins by enhancing dimerization. Science. 1993;262(5132):395-9.