Skip to main content
SpringerLink
Log in

Effects of HIV-1 nef on cellular gene expression profiles

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

The early human immunodeficiency virus (HIV) accessory protein Nef makes an important contribution to virulence, but the mechanisms by which Nef influences pathogenesis remain unclear. Many well-studied effects of Nef, like CD4 and class I MHC downregulation, occur posttranslationally. However, Nef has the potential to affect gene expression by interfering with cell signaling pathways and by virtue of structural features such as the Pro-X-X-Pro motif, which may interact withsrc homology region-3 domains of src-like kinases. We used a cDNA microarray screening strategy to identify cellular genes whose steady state transcriptional levels may be affected by Nef. We generated HeLa cell lines expressing wild-type or mutant HIV-1nef protein sequences. Using cDNA microarray technology, we compared the patterns of cellular gene expression in the various cell lines to the pattern in non-Nef-expressing HeLa cells. By matching the patterns of cellular gene expression in HeLa cell lines expressing various Nefs with that of parental HeLa cells, we identified several cellular genes whose expression was modulated differentially by Nef and its mutants. We confirmed the differential expression of selected genes by RNA filter blotting. Genes expressed at higher levels included proteases, transcription factors, protein kinases, nuclear import/export proteins, adaptor molecules and cyclins, some of which have previously been implicated as being important for HIV replication and pathogenesis. The results indicate that Nef expression can alter the expression of cellular genes and suggest that this alteration in cellular gene expression may serve to optimize the cell to support the subsequent stages of viral replication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aiken C, Konner J, Landau NR, Lenburg ME, Torono D. Nef induces CD4 endocytosis: Requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Cell 76:853–864;1994.

    Google Scholar 

  2. Amundson SA, Bittner M, Chen Y, Trent J, Meltzer P, Fornace AJ Jr. Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses. Oncogene 18:3666–3672;1999.

    Google Scholar 

  3. Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WJ, Hunter T, Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature 332:166–171;1988.

    Google Scholar 

  4. Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072:129–157;1991.

    Google Scholar 

  5. Aso T, Haque D, Barstead RJ, Conaway RC, Conaway JW. The inducible elongin A elongation activation domain: Structure, function and interaction with the elongin BC complex. EMBO J 15:5557–5566;1996.

    Google Scholar 

  6. Aso T, Haque D, Fukudome K, Brower CS, Conaway JW, Conaway RC. A human cDNA encoding the 110-kDa A subunit of RNA polymerase II transcription factor elongin. Gene 168:277–298;1996.

    Google Scholar 

  7. Aso T, Lane WS, Conaway JW, Conaway RC. Elongin (SIII): A multisubunit regulator of elongation by RNA polymerase II (see comments). Science 269:1439–1443;1995.

    Google Scholar 

  8. Barker HM, Brewis ND, Street AJ, Spurr NK, Cohen PT. Three genes for protein phosphatase 1 map to different human chromosomes: Sequence, expression and gene localisation of protein serine/threonine phosphatase 1 beta (PPP1CB). Biochim Biophys Acta 1220:212–218;1994.

    Google Scholar 

  9. Barnabas S, Hai T, Andrisani OM. The hepatitis B virus X protein enhances the DNA binding potential and transcription efficacy of bZip transcription factors. J Biol Chem 272:20684–20690;1997.

    Google Scholar 

  10. Baur AS, Sawai ET, Dazin P, Fantl WJ, Cheng-Mayer C, Peterlin BM. HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. Immunity 1:373–384;1994.

    Google Scholar 

  11. Beeler JF, LaRochelle WJ, Chedid M, Tronick SR, Aaronson SA. Prokaryotic expression cloning of a novel human tyrosine kinase. Mol Cell Biol 14:982–988;1994.

    Google Scholar 

  12. Belaaouaj A, Shipley JM, Kobayashi DK, Zimonjic DB, Popescu N, Silverman GA, Shapiro SD. Human macrophage metaolloelastase. Genomic organization, chromosomal location, gene linkage, and tissue-specific expression. J Biol Chem 270:14568–14575;1995.

    Google Scholar 

  13. Benichou S, Bomsel M, Bodeus M, Durand H, Doute M, Letourneur F, Camonis J, Benarous R. Physical interaction of the HIV-1 Nef protein with beta-COP, a component of non-clathrin-coated vesicles essential for membrane traffic. J Biol Chem 269:30073–30076;1994.

    Google Scholar 

  14. Benson RE, Sanfridson A, Ottinger JS, Doyle C, Cullen BR. Downregulation of cell-surface CD4 expression by simian immunodeficiency virus Nef prevents viral super infection. J Exp Med 177:1561–1566;1993.

    Google Scholar 

  15. Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK, Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 238:1386–1392;1987.

    Google Scholar 

  16. Bradham DM, Igarashi A, Potter RL, Grotendorst GR. Connective tissue growth factor: A cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol 114:1285–1294;1991.

    Google Scholar 

  17. Brinkmann U. CAS, the human homologue of the yeast chromosome-segregation gene CSE1, in proliferation, apoptosis, and cancer. Am J Hum Genet 62:509–513;1998.

    Google Scholar 

  18. Brinkmann U, Brinkmann E, Gallo M, Pastan I. Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1. Proc Natl Acad Sci USA 92:10427–10431;1995.

    Google Scholar 

  19. Brinkmann U, Brinkmann E, Gallo M, Scherf U, Pastan I. Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis. Biochemistry 35:6891–6899;1996.

    Google Scholar 

  20. Caldwell JE, Waddle JA, Cooper JA, Hollands JA, Casella SJ, Casella JF. cDNAs encoding the beta subunit of cap Z, the actin-capping protein of the Z line of muscle. J Biol Chem 264:12648–12652;1989.

    Google Scholar 

  21. Casella JR, Barron-Casella EA, Torres MA. Quantitation of Cap Z in conventional actin preparations and methods for further purification of actin. Cell Motil Cytoskeleton 30:164–170;1995.

    Google Scholar 

  22. Casella JF, Casella SJ, Hollands JA, Caldwell JE, Cooper JA. Isolation and characterization of cDNA encoding the alpha subunit of Cap Z(36/32), an actin-capping protein from the Z line of skeletal muscle. Proc Natl Acad Sci USA 86:5800–5804;1989.

    Google Scholar 

  23. Chen Y, Dougherty E, Bittner M. Ratio-based decision and quantitative analysis of cDNA microarray images. J Biomed Opt 1:364–374;1997.

    Google Scholar 

  24. Chowers MY, Pandori MW, Spina CA, Richman DD, Guatelli JC. The growth advantage conferred by HIV-1 nef is determined at the level of viral DNA formation and is independent of CD4 downregulation. Virology 212:451–457;1995.

    Google Scholar 

  25. Chowers MY, Spina CA, Kwoh TJ, Fitch NJ, Richman DD, Guatelli JC. Optimal infectivity in vitro of human immunodeficiency virus type 1 requires an intact nef gene. J Virol 68:2906–2914;1994.

    Google Scholar 

  26. Cirino G, Flower RJ, Browning JL, Sinclair LK, Pepinsky RB: Recombinant human lipocortin 1 inhibits thromboxane release from guinea-pig isolated perfused lung. Nature 328:270–272;1987.

    Google Scholar 

  27. Collette Y, Dutartre H, Benziane A, Ramos M, Benarous R, Harris M, Olive D. Physical and functional interaction of Nef with Lck. HIV-1 Nef-induced T-cell signaling defects. J Biol Chem 271:6333–6341;1996.

    Google Scholar 

  28. Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391:397–401;1998.

    Google Scholar 

  29. Colwill K, Pawson T, Andrews B, Prasad J, Manley JL, Bell JC, Duncan PI. The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. EMBO J 15:265–275;1996.

    Google Scholar 

  30. D'Arpa P, Machlin PS, Ratrie H 3rd, Rothfield NF, Cleveland DW, Earnshaw WC. cDNA cloning of human DNA topoisomerase I: Catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc Natl Acad Sci USA 85:2543–2547:1988.

    Google Scholar 

  31. Decroly E, Vandenbranden M, Ruysschaert JM, Cogniaux J, Jacob GS, Howard SC, Marshall G, Kompelli A, Basak A, Jean F, et al. The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM). J Biol Chem 269:12240–12247;1994.

    Google Scholar 

  32. Decroly E, Wouters S, Di Bello C, Lazure C, Ruysschaert J, Seidah NG. Identification of the paired basic convertases implicated in HIV gp160 processing based on in vitro assays and expression in CD4(+) cell lines. J Biol Chem 271:30442–30450;1996.

    Google Scholar 

  33. DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM. Use of a cDNA microarray to analyse gene expression patterns in humans cancer. Nat Genet 14:457–460;1996.

    Google Scholar 

  34. Ding H, Benotmane AM, Suske G, Collen D, Belayew A. Functional interactions between Sp1 or Sp3 and the helicase-like transcription factor mediate basal expression from the human plasminogen activator inhibitor-1 gene. J Biol Chem 274:19573–19580;1999.

    Google Scholar 

  35. Du Z, Lang SM, Sasseville VG, Lackner AA, Ilyinskii PO, Daniel MD, Jung JU, Desrosiers RC. Identification of a nef allele that causes lymphocyte activation and acute disease in macaque monkeys. Cell 82:665–674;1995.

    Google Scholar 

  36. Duden R, Griffiths G, Frank R, Argos P, Kreis TE. Beta-COP, a 110 kd protein associated with non-clathrin-coated vesicles and the Golgi complex, shows homology to beta-adaptin. Cell 64:649–665;1991.

    Google Scholar 

  37. Fackler OT, d'Aloja P, Baur AS, Federico M, Peterlin BM. Nef from human immunodeficiency virus type 1(F12) inhibits viral production and infectivity. J Virol 75:6601–6608;2001.

    Google Scholar 

  38. Fackler OT, Lu X, Frost JA, Geyer M, Jiang B, Luo W, Abo A, Alberts AS, Peterlin BM. p21-activated kinase 1 plays a critical role in cellular activation by Nef. Mol Cell Biol 20:2619–2627;2000.

    Google Scholar 

  39. Flower RJ, Rothwell NJ. Lipocortin-1: Cellular mechanisms and clinical relevance. Trends Pharmacol Sci 15:71–76;1994.

    Google Scholar 

  40. Fornerod M, Ohno M, Yoshida M, Mattaj I. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell 90:1051–1060;1997.

    Google Scholar 

  41. Foster JL, Anderson SJ, Frazier AL, Garcia JV. Specific suppression of human CD4 surface expression by Nef from the pathogenic simian immunodeficiency virus SIV mac239open. Virology 201:373–379;1994.

    Google Scholar 

  42. Garcia JV, Miller AD. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature 350:508–511;1991.

    Google Scholar 

  43. Gonzalez P, Rao PV, Zigler JS Jr. Molecular cloning and sequencing of zeta-crystallin/quinone reductase cDNA from human liver. Biochem Biophys Res Commun 191:902–907;1993.

    Google Scholar 

  44. Gorlich D, Hartmann E, Prehn S, Rapoport TA. A protein of the endoplasmic reticulum involved early in polypeptide translocation. Nature 357:47–52;1992.

    Google Scholar 

  45. Graziani A, Galimi F, Medico E, Cottone E, Gramaglia D, Boccaccio C, Comoglio PM. The HIV-1 nef protein interferes with phosphatidy-linositol 3-kinase activation. J Biol Chem 271:6590–6593;1996.

    Google Scholar 

  46. Greenway A, Azad A, McPhee D. Human immunodeficiency virus type 1 Nef protein inhibit activation pathways in peripheral blood mononuclear cells and T-cell lines. J Virol 69:1842–1850;1995.

    Google Scholar 

  47. Gupta M, Fujimori A, Pommier Y. Eukaryotic DNA topoisomerases I. Biochim Biophys Acta 1262:1–14;1995.

    Google Scholar 

  48. Hahn FM, Xuan JW, Chambers AF, Poulter CD. Human isopentenyl disphosphate:dimethylallyl diphosphate isomerase: Overproduction, purification, and characterization. Arch Biochem Biophys 332:30–34;1996.

    Google Scholar 

  49. Hai TW, Liu F, Coukos WJ, Green MR. Transcription factor ATF cDNA clones: An extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev 3:2083–2090;1989.

    Google Scholar 

  50. Hattori K, Angel P, Leu Beau MM, Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc Natl Acad Sci USA 85:9148–9152;1988.

    Google Scholar 

  51. Hegde RS, Voigt S, Rapoport TA, Lingappa VR. TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum. Cell 92:621–631;1998.

    Google Scholar 

  52. Heiland S, Knippers R. The human topoisomerase I gene promoter is regulated by NF-IL6. Mol Cell Biol 15:6623–6631;1995.

    Google Scholar 

  53. Henderson BR, Percipalle P. Interactions between HIV Rev and nuclear import and export factors: The Rev nuclear localisation signal mediates specific binding to human importin-beta. J Mol Biol 274:693–707;1997.

    Google Scholar 

  54. Iafrate AJ, Bronson S, Skowronski J. Separable functions of Nef disrupt two aspects of T cell receptor machinery: CD4 expression and CD3 signaling. EMBO J 16:673–684;1997.

    Google Scholar 

  55. Imanaka T, Aihara K, Takano T, Yamashita A, Sato R, Suzuki Y, Yokota S, Osumi T. Characterization of the 70-kDa peroxisomal membrane protein, an ATP binding cassette transporter. J Biol Chem 274:11968–11976;1999.

    Google Scholar 

  56. Johnson KW, Smith KA. Molecular cloning of a novel human cdc2/CDC28-like protein kinase. J Biol Chem 266:3402–3407;1991.

    Google Scholar 

  57. Juan CC, Hwang JL, Liu AA, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Zhang H, Wang JC, Liu LF. Human DNA topoisomerase I is encoded by a single-copy gene that maps to chromosome region 20q12-13.2. Proc Natl Acad Sci USA 85:8910–8913;1988.

    Google Scholar 

  58. Kestler HW 3rd, Ringler DJ, Mori K, Panicali DL, Sehgal PK, Daniel MD, Desrosiers RC. Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65:651–662;1991.

    Google Scholar 

  59. Khan IH, Sawai ET, Antonio E, Weber CJ, Mandell CP, Montbriand P, Luciw PA. Role of the SH3-ligand domain of simian immunodeficiency virus Nef in interaction with Nef-associated kinase and simian AIDS in rhesus macaques. J Virol 72:5820–5830;1998.

    Google Scholar 

  60. Khan J, Simon R, Bittner M, Chen Y, Leighton SB, Pohida T, Smith PD, Jiang Y, Gooden GC, Trent JM, Meltzer PS. Gene expression profiling of alveolar rhabdomyosarcoma with cDNA microarrays. Cancer Res 58:5009–5013;1998.

    Google Scholar 

  61. Kim HS, Nagalla SR, Oh Y, Wilson E, Roberts CT Jr. Rosenfeld RG. Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): Characterization of connective tissue growth factor as a member of the IGFBP superfamily. Proc Natl Acad Sci USA 94:12981–12986;1997.

    Google Scholar 

  62. Kim SB, Yang WS, Lee OS, Lee KP, Park JS, Na DS. Lipocortin-1 inhibitis proliferation of cultured human mesangial cells. Nephron 74:39–44;1996.

    Google Scholar 

  63. Kim T, Mudry RA Jr, Rexrode CA 2nd, Pathak VK. Retroviral mutation rates and A-to-G hypermutations during different stages of retroviral replication. J Virol 70:7594–7602;1996.

    Google Scholar 

  64. Kotov A, Zhou J, Flicker P, Aiken C. Association of Nef with the human immunodeficiency virus type 1 core. J Virol 73:8824–8830;1999.

    Google Scholar 

  65. Kudo N, Khochbin S, Nishi K, Kitano K, Yanagida M, Yoshida M, Horinouchi S. Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins. J Biol Chem 272:29742–29751;1997.

    Google Scholar 

  66. Kutay U, Bischoff FR, Kostka S, Kraft R, Gorlich D. Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor. Cell 90:1061–1071;1997.

    Google Scholar 

  67. Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M, et al. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225;1993.

    Google Scholar 

  68. Lee MG, Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327:31–35;1987.

    Google Scholar 

  69. Luria S, Chambers I, Berg P. Expression of the type I human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. Proc Natl Acad Sci USA 88:5326–5330;1991.

    Google Scholar 

  70. Maddon PJ, McDougal JS, Clapham PR, Dalgleish AG, Jamal S, Weiss RA, Axel R. HIV infection does not require endocytosis of its receptor, CD4. Cell 54:865–874;1988.

    Google Scholar 

  71. Maldarelli F, Xiang C, Chamoun G, Zeichner SL. The expression of the essential nuclear splicing factor SC35 is altered by human immunodeficiency virus infection. Virus Res 53:39–51;1998.

    Google Scholar 

  72. Marsh M, Pelchen-Matthews A. Endocytic and exocytic regulation of CD4 expression and function. Curr Top Microbiol Immunol 205:107–135;1996.

    Google Scholar 

  73. Martinerie C, Viegas-Pequignot E, Guenard I, Dutrillaux B, Nguyen VC, Bernheim A, Perbal B. Physical mapping of human loci homologous to the chicken nov proto-oncogene. Oncogene 7:2529–2534;1992.

    Google Scholar 

  74. McCune JM, Rabin LB, Feinberg MB, Lieberman M, Kosek JC, Reyes GR, Weissman IL. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell 53:55–67;1988.

    Google Scholar 

  75. Miller MD, Warmerdam MT, Gaston I, Greene WC, Feinberg MB. The human immunodeficiency virus-1 nef gene product: A positive factor for viral infection and replication in primary lymphocytes and macrophages. J Exp Med 179:101–113;1994.

    Google Scholar 

  76. Narkewicz MR, Sauls SD, Tjoa SS, Teng C, Fennessey PV. Evidence for intracellular partitioning of serine and glycine metabolism in Chinese hamster ovary cells. Biochem J 313:991–996;1996.

    Google Scholar 

  77. Ng PW, Iha H, Iwanaga Y, Bittner M, Chen Y, Jiang Y, Gooden G, Trent JM, Meltzer P, Jeang KT, Zeichner SL. Genome-wide expression changes induced by HTLV-1 Tax: Evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappaB activation. Oncogene 20:4484–4496;2001.

    Google Scholar 

  78. Niederman TM, Hastings WR, Ratner L. Myristoylation-enhanced binding of the HIV-1 Nef protein to T cell skeletal matrix. Virology 197;420–425;1993.

    Google Scholar 

  79. Ohagi S, Sakaguchi H, Sanke T, Tatsuta H, Hanabusa T, Najo K. Human prohormone convertase 3 gene: Exon-intron organization and molecular scanning for mutations in Japanese subjects with NIDDM. Diabetes 45:897–901;1996.

    Google Scholar 

  80. Pandori MW, Fitch NJ, Craig HM, Richman DD, Spina CA, Guatelli JC. Producer-cell modification of human immunodeficiency virus type 1: Nef is a virion protein. J Virol 70:4283–4290;1996.

    Google Scholar 

  81. Perretti M, Flower RJ. Modulation of IL-1-induced neutrophil migration by dexamethasone and lipocortin 1. J Immunol 150:992–999;1993.

    Google Scholar 

  82. Peter F, Plutner H, Zhu H, Kreis TE, Balch WE. Beta-COP is essential for transport of protein from the endoplasmic reticulum to the Golgi in vitro. J Cell Biol 122:1155–1167;1993.

    Google Scholar 

  83. Peters C, Andrews PD, Stark MJ, Cesaro-Tadic S, Glatz A, Podtelejnikov A, Mann M, Mayer A. Control of the terminal step of intracellular membrane fusion by protein phosphatase 1. Science 285:1084–1087;1999.

    Google Scholar 

  84. Pfendner W, Pizer LI. The metabolism of serine and glycine in mutant lines of Chinese hamster ovary cells. Arch Biochem Biophys 200:503–512;1980.

    Google Scholar 

  85. Piguet V, Gu F, Foti M, Demaurex N, Gruenberg J, Carpentier JL, Trono D. Nef-induced CD4 degradation: A diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 97:63–73;1999.

    Google Scholar 

  86. Saksela K, Cheng G, Baltimore D. Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4. EMBO 14:484–491;1995.

    Google Scholar 

  87. Sasaki K, Shima H, Kitagawa Y, Irino S, Sugimura T, Nagao M. Identification of members of the protein phosphatase 1 gene family in the rat and enhanced expression of protein phosphatase 1 alpha gene in rat hepatocellular carcinomas. Jpn J Cancer Res 81:1272–1280;1990.

    Google Scholar 

  88. Schena M, Shalon D, Davis RW, Brown PO. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270:467–470;1995.

    Google Scholar 

  89. Schwartz O, Marechal V, Danos O, Heard JM. Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell. J Virol 69:4053–4059;1995.

    Google Scholar 

  90. Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 2:338–342;1996.

    Google Scholar 

  91. Semba K, Yamanashi Y, Nishizawa M, Sukegawa J, Yoshida M, Sasaki M, Yamamoto T, Toyoshima K. Location of the c-yes gene on the human chromosome and its expression in various tissues. Science 227:1038–1040;1985.

    Google Scholar 

  92. Shapiro SD, Kobayashi DK, Ley TJ. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem 268:23824–23829;1993.

    Google Scholar 

  93. Shimo T, Nakanishi T, Nishida T, Asano M, Kanyama M, Kuboki T, Tamatani T, Tezuka K, Takemura M, Matsumura T, Takigawa M. Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo. J Biochem (Tokyo) 126:137–145;1999.

    Google Scholar 

  94. Shykind BM, Kim J, Stewart L, Champoux JJ, Sharp PA. Topoisomerase I enhances TFIID-TFIIA complex assembly during activation of transcription. Genes Dev 11:397–407;1997.

    Google Scholar 

  95. Simmons A, Aluvihare V, McMichael A. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity 14:763–777;2001.

    Google Scholar 

  96. Sorbara LR, Maldarelli F, Chamoun G, Schilling B, Chokekijcahi S, Staudt L, Mitsuya H, Simpson IA, Zeichner SL. Human immunodeficiency virus type 1 infection of H9 cells induces increased glucose transporter expression. J Virol 70:7275–7279;1996.

    Google Scholar 

  97. Spina CA, Kwoh TJ, Chowers MY, Guatelli JC, Richman DD. The importance of Nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes. J Exp Med 179:115–123;1994.

    Google Scholar 

  98. Stover PJ, Chen LH, Suh JR, Stover DM, Keyomarsi K, Shane B. Molecular cloning, characterization, and regulation of the human mitochondrial serine hydroxymethyltransferase gene. J Biol Chem 272:1842–1848;1997.

    Google Scholar 

  99. Sukegawa J, Semba K, Yamanashi Y, Nishizawa M, Miyajima N, Yamamoto T, Toyoshima K. Characterization of cDNA clones for the human c-yes gene. Mol Cell Biol 7:41–47;1987.

    Google Scholar 

  100. Truant R, Cullen BR. The arginine-rich domains present in human immunodeficiency virus type 1 Tat and Rev function as direct import in beta-dependent nuclear localization signals. Mol Cell Biol 19:1210–1217;1999.

    Google Scholar 

  101. Vollenweider F, Benjannet S, Decroly E, Savaria D, Lazure C, Thomas G, Chretien M, Seidah NG. Comparative cellular processing of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 by the mammalian subtilisin/kexin-like convertases. Biochem J 314:521–532;1996.

    Google Scholar 

  102. Wallner BP, Mattaliano RJ, Hession C, Cate RL, Tizard R, Sinclair LK, Foeller C, Chow EP, Browing JL, Ramachandran KL, et al. Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature 320:77–81;1986.

    Google Scholar 

  103. Wang J. DNA topoisomerases. Annu Rev Biochem 65:635–692;1996.

    Google Scholar 

  104. Watanabe Y, Kawakami K, Hirayama Y, Nagano K. Transcription factors positively and negatively regulating the Na,K-ATPase alpha 1 subunit gene. J Biochem (Tokyo) 114:849–855;1993.

    Google Scholar 

  105. Weeks BS. The role of HIV-1 activated leukocyte adhesion mechanisms and matrix metalloproteinase secretion in AIDS pathogenesis. Int J Mol Med 1:361–366;1998.

    Google Scholar 

  106. Weeks BS, Klotman ME, Holloway E, Stetler-Stevenson WG, Kleinman HK, Klotman PE. HIV-1 infection stimulates T cell invasiveness and synthesis of the 92-kDa type IV collagenase. AIDS Res Hum Retroviruses 9:513–518;1993.

    Google Scholar 

  107. Whitmarsh AJ, Davis RJ. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 74:589–607;1996.

    Google Scholar 

  108. Williams TM, Moolten D, Burlein J, Romano J, Bhaerman R, Godillot A, Mellon M, Rauscher FJ 3rd, Kant JA. Identification of a zinc finger protein that inhibits IL-2 gene expression. Science 254:1791–1794;1991.

    Google Scholar 

  109. Xuan JW, Kowalski J, Chambers AF, Denhardt DT. A human promyelocyte mRNA transiently induced by TPA is homologous to yeast IPP isomerase. Genomics 20:129–131;1994.

    Google Scholar 

  110. Yu G, Felsted RL. Effect of myristoylation on p27 nef subcellular distribution and suppression of HIV-LTR transcription. Virology 187:46–55;1992.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, USA

    Ana Petrovic & Sundararajan Venkatesan

  2. Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., USA

    Michael Bittner, Paul Meltzer & Jeffrey Trent

  3. 10S255, Building 10, HAMB, NCI, NIH, 10 Center Drive, 20892, Bethesda, MD, USA

    Syed Shaheduzzaman, Vyjayanthi Krishnan & Steven Zeichner

Authors
  1. Syed Shaheduzzaman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vyjayanthi Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Petrovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Bittner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeffrey Trent
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sundararajan Venkatesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Steven Zeichner
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

S.S. and V.K. contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shaheduzzaman, S., Krishnan, V., Petrovic, A. et al. Effects of HIV-1 nef on cellular gene expression profiles. J Biomed Sci 9, 82–96 (2002). https://doi.org/10.1007/BF02256581

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02256581

Key Words

Search

Navigation