The HIV-1 Tat Transactivator Contains an Arginine-Glycine-Aspartyl (RGD) Cell Adhesion Site

  • David A. Brake
  • Christine Debouck
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Since the discovery of HIV-1 as the etiologic agent of acquired immunodeficiency syndrome (Barre-Sinoussi et al, 1983; Gallo et al, 1984), enormous progress has been made toward understanding this virus organization and its life cycle within target cells. HIV-1 has been shown to have the same 5′ LTR-qaq-pol-env-LTR 3′ genomic structure as the classical avian and murine retroviruses (Figure 1; Ratner et al, 1985; Wain-Hobson et a1,1985; Sanchez-Pescador et al, 1985; Muesing et al, 1985). It is therefore logical that early studies on HIV-1 focused on its gag, pol and env gene products for diagnostic, therapeutic and prophylactic purposes. Naturally, these initial studies greatly benefited from the knowledge accumulated over the years on the avian and murine systems (Weiss et al, 1982). In the therapeutic area, HIV-1 reverse transcriptase and later HIV-1 protease have been the object of intense investigations and inhibitor discovery efforts that have been reviewed recently (Goff, 1990; Debouck and Metcalf, 1990).


Human Immunodeficiency Virus Type Long Terminal Repeat Human Immune Deficiency Virus Equine Infectious Anemia Virus Cell Adhesion Site 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aldovini, A., Debouck, C., Feinberg, M.B., Rosenberg, M., Arya, S.K., and Wong-Staal, F., 1986, Synthesis of the complete trans-activation gene product of human T-lymphotropic virus type III in Escherichia coli, Proc. Natl. Acad. Sci. USA 83:6672.Google Scholar
  2. Arya, S.K., Guo, C., Josephs, S.F., and Wong-Staal, F., 1985, Transactivator gene of human T-lymphotropic virus type III (HTLVIII), Science, 229: 69.PubMedCrossRefGoogle Scholar
  3. Barre-Sinoussi, F., Chermann, J.C., Rey, R., Nugeyre, M.T., Chamaret, S., Gruest, J., Dauguet, C., Axler-Blin, C., Brun-Vezinet, F., Rouzioux, C., Rozenbaum, W., and Montagnier, L., 1983, Isolation of a Tlymphotropic retrovirus from a patient at risk for acquired immunodeficiency syndrome (AIDS), Science, 220: 868.PubMedCrossRefGoogle Scholar
  4. Biesecker, G., 1990, The complement SC5b-9 complex mediates cell adhesion through a vitronectin receptor, J. Immunol., 145: 209.PubMedGoogle Scholar
  5. Brake, D.A., Debouck, C., and Biesecker, G., 1990, Identification of an Arg-Gly-Asp (RGD) cell adhesion site in human immunodeficiency virus type 1 transactivation protein, tat, J. Cell Biol., 111: 1275.Google Scholar
  6. Brake, D.A., Goudsmit, J., Krone, W.J.A., Schammel, P., Appleby, A., Meloen, R.H., and Debouck, C., 1990, Characterization of murine monoclonal antibodies to the tat protein from human immunodeficiency virus type 1, J. Virol, 64: 962.PubMedGoogle Scholar
  7. Cullen, B.R., and Greene, W.C., 1990, Functions of the auxiliary gene products of the human immunodeficiency virus type 1, Virology, 178: 1.PubMedCrossRefGoogle Scholar
  8. Davis, J.L., Molineaux, S., and Clements, J.E., 1987, Visna virus exhibits a complex transcriptional pattern: one aspect of gene expression shared with the acquired immunodeficiency syndrome retrovirus, J. Viral., 61: 1325.Google Scholar
  9. Dayton, A.I., Sodroski, J.G., Rosen, C.A., Goh, W.C., and Haseltine, W.A., 1986, The transactivator gene of the human T cell lymphotropic virus type III is required for replication, Cell, 44: 941.PubMedCrossRefGoogle Scholar
  10. Debouck, C., and Metcalf, B.W., 1990, Human immunodeficiency virus protease: a target for AIDS therapy, Drug Dev. Res. 20: in press.Google Scholar
  11. Dorn, P.L., and Derse, D., 1988, Cis-and trans-acting regulation of gene expression of equine infectious anemia virus, J. Virol. 62, 3522.Google Scholar
  12. Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C., and 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.Google Scholar
  13. Fisher, A.G., Feinberg, M.B., Josephs, S.F., Harper, M.E., Marselle, L.M., Reyes, G., Gonda, M.A., Aldovini, A., Debouck, C., Gallo, R.C., and Wong-Staal, F., 1986, The trans-activator gene of HTLV-III is essential for virus replication, Nature, 320: 367.PubMedCrossRefGoogle Scholar
  14. Frankel, A.D. and Pabo, C.O., 1988, Cellular uptake of the tat protein from human immunodeficiency virus, Cell, 55: 1189.PubMedCrossRefGoogle Scholar
  15. Frankel, A.D., Biancalana, S. and Hudson, D., 1989, Activity of synthetic peptides from the tat protein of human immunodeficiency virus type 1, Proc. Natl. Acad. Sci. USA, 86: 7397.PubMedCrossRefGoogle Scholar
  16. Gallo, R.C., Salahuddin, S.Z., Popovic, M., Shearer, G.M., Kaplan, M., Haynes, B.F., Palker, T.J., Redfield, R., Oleske, J., Safai, B., White, G., Foster, R. amnd Markham, P., 1984, Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS, Science, 224: 500.PubMedCrossRefGoogle Scholar
  17. Green, M. and Lowenstein, P.M., 1988, Autonomous functional domains of chemically synthesized human immunodeficiency tat trans-activator protein, Cell, 55: 1179.PubMedCrossRefGoogle Scholar
  18. Goff, S.P., 1990, Retroviral reverse transcriptase: synthesis, structure, and function, J. Acq. Imm. Def. Syn., 3: 817.Google Scholar
  19. Kikukawa, R., Koyanagi, Y., Harada, S., Kobayashi, N., Hatanaka, M., and Yamamoto, N., 1986, Differential susceptibility to the acquired immunodeficiency syndrome retrovirus in cloned cells of human leukemic T-cell line Molt-4, J.Virol., 57: 1159.Google Scholar
  20. Leis, J., Baltimore, D., Bishop, J.M., Coffin, J., Fleissner, E., Goff, S.P., Oroszlan, S., Robinson, H., Skalka, A.M., Temin, H.M., and Vogt, V., 1988, Standardized and simplified nomenclature for proteins common to all retroviruses, J. Virol., 62: 1808.Google Scholar
  21. Levy, J.A., Hoffman, A.D., Kramer, S.M., Landis, J.A., Shimabukuru, J.M., and Oshiro, L.S., 1984, Isolation of lymphocytopathic retroviruses from SanFrancisco patients with AIDS, Science, 235: 840.CrossRefGoogle Scholar
  22. Mikovits, J.A., Raziuddin, Gonda, M., Ruta, M., Lohrey, N.C., Kung, H.-F., and Ruscetti, F.W., 1990, Negative regulation of human immune deficiency virus replication in monocytes. Distinction between restricted and latent expression in THP-1, J. Exp. Med., 171: 1705.Google Scholar
  23. Mitsuya, H., Weinhold, K.J., Furman, P.A., St. Clair, M.H., Lehrman, S.N., Gallo, R.C., Bolognesi, D., Barry, D.W., and Broder, S., 3’Azido-3’-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro, Proc. Natl. Acad. Sci. USA, 82: 7096.Google Scholar
  24. Muesing, M.A,., Smith, D.H., Cabradilla, C.D., Benton, C.V., Lasky, L.A., and Capon, D.J., 1985, Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus, Nature, 313: 450.CrossRefGoogle Scholar
  25. Nelbock, P., Dillon, P.J., Perkins, A., and Rosen, C.A., 1990, A cDNA for a protein that interacts with the human immunodeficiency virus tat transactivator, Science, 248: 1650.PubMedCrossRefGoogle Scholar
  26. Obara, M., Kang, M.S., Yamada, K.M., 1988, Site-directed mutagenesis of the cell-binding domain of human fibronectin: separable, synergistic sites mediate adhesive function, Cell, 53: 649.PubMedCrossRefGoogle Scholar
  27. Ratner, L., Haseltine, W., Patarca, R., Livak, K.J., Starcich, B., Josephs, S.F., Doran, E.R., Rafalski, J.A., Whitehorn, E.A., Baumeister, K., Ivanoff, L., Petteway, S.R., Pearson, M.L., Lautenberger, J.A., Papas, T.S., Ghrayeb, J., Chang, N.T., Gallo, R.C., and Wong-Staal, F., 1985, Complete nucleotide sequence of the AIDS virus, HTLV-III, Nature, 313: 277.PubMedCrossRefGoogle Scholar
  28. Rosen, C.A., and Pavlakis, G.N., 1990, Tat and Rev: positive regulators of HIV gene expression, AIDS, 4: 499.PubMedCrossRefGoogle Scholar
  29. Ruoslahti, E., and Pierschbacher, M.D., 1987, New perspectives in cell adhesion: RGD and integrins, Science, 238: 491.PubMedCrossRefGoogle Scholar
  30. Sanchez-Pescador, R., Power, M.D., Barr, P.J., Steimer, K.S., Stempien, M.M., Brown-Shimer, S.L., Gee, W.W., Renard, A., Randolph, A., Levy, J.A., Dina, D., and Luciw, P.A., 1985, Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2), Science, 227: 484.PubMedCrossRefGoogle Scholar
  31. Sodroski, J., Patarca, R., Rosen, C., Wong-Staal, F., and Haseltine, W., 1985, Location of the trans-activation region on the genome of human T-cell lymphotropic virus type III, Science, 229: 74.PubMedCrossRefGoogle Scholar
  32. Vogel, J., Hinrich, S.H., Reynolds, R.K., Luciw, P.A., and Jay, G., 1988, The HIV tat gene induces dermal lesions resembling Kaposi’s sarcoma in transgenic mice, Nature (Lond.), 335: 606.CrossRefGoogle Scholar
  33. Wain-Hobson, S., Sonigo, P., Danos, O., Cole, S., and Alizon, M., 1985, Nucleotide sequence of the AIDS virus, LAV, Cell, 40: 9.PubMedCrossRefGoogle Scholar
  34. Weiss, R., Teich, N., Varmus, H., and Coffin, J. (eds), 1982, “Molecular biology of tumor viruses, Cold Spring Harbor Laboratory”, Cold Spring Harbor, NY.Google Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • David A. Brake
    • 1
  • Christine Debouck
    • 1
  1. 1.Department of Molecular GeneticsSmithKline Beecham PharmaceuticalsKing of PrussiaUSA

Personalised recommendations