Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1996 Jun;70(6):4009–4016. doi: 10.1128/jvi.70.6.4009-4016.1996

Repression of human immunodeficiency virus type 1 long terminal repeat-driven gene expression by binding of the virus to its primary cellular receptor, the CD4 molecule.

P Bérubé 1, B Barbeau 1, R Cantin 1, R P Sékaly 1, M Tremblay 1
PMCID: PMC190279  PMID: 8648738

Abstract

We have previously postulated that the binding of the human immunodeficiency virus type 1 (HIV-1) to cell surface CD4 induces signal transduction pathways that down-modulate production of progeny virions in acutely infected T cells (M. Tremblay, S. Meloche, S. Gratton, M. A. Wainberg, and R.-P. Sékaly, EMBO J. 13:774-783, 1994). To evaluate the possibility that CD4 cross-linking might indeed affect viral gene expression, we have introduced a molecular construct made of the luciferase reporter gene placed under the control of the regulatory elements of HIV-1 in several CD4-positive T-cell lines. We found that cross-linking of CD4 with defective HIV-1 particles and heat-inactivated viruses inhibits long terminal repeat-dependent luciferase expression. Experiments revealed that the gp120-CD4 interaction was necessary to repress HIV-1 long terminal repeat-dependent luciferase activity. The cytoplasmic domain of CD4 was also found to be required for this effect to occur. The virus-mediated signal transduction was shown to be mediated via p56lck-dependent and -independent pathways. These results indicate that the earliest event in the HIV-1 replicative cycle, namely, the binding of the virus to its cellular receptor, can lead to signal transduction culminating in down-modulation of viral gene expression. Thus we propose that defective viruses could regulate the pathogenesis of HIV disease as they constitute the vast majority of circulating HIV-1 particles.

Full Text

The Full Text of this article is available as a PDF (594.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilar-Cordova E., Chinen J., Donehower L., Lewis D. E., Belmont J. W. A sensitive reporter cell line for HIV-1 tat activity, HIV-1 inhibitors, and T cell activation effects. AIDS Res Hum Retroviruses. 1994 Mar;10(3):295–301. doi: 10.1089/aid.1994.10.295. [DOI] [PubMed] [Google Scholar]
  2. Arya S. K., Guo C., Josephs S. F., Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69–73. doi: 10.1126/science.2990040. [DOI] [PubMed] [Google Scholar]
  3. Bank I., Chess L. Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med. 1985 Oct 1;162(4):1294–1303. doi: 10.1084/jem.162.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benkirane M., Corbeau P., Housset V., Devaux C. An antibody that binds the immunoglobulin CDR3-like region of the CD4 molecule inhibits provirus transcription in HIV-infected T cells. EMBO J. 1993 Dec 15;12(13):4909–4921. doi: 10.1002/j.1460-2075.1993.tb06185.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benkirane M., Hirn M., Carrière D., Devaux C. Functional epitope analysis of the human CD4 molecule: antibodies that inhibit human immunodeficiency virus type 1 gene expression bind to the immunoglobulin CDR3-like region of CD4. J Virol. 1995 Nov;69(11):6898–6903. doi: 10.1128/jvi.69.11.6898-6903.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benkirane M., Jeang K. T., Devaux C. The cytoplasmic domain of CD4 plays a critical role during the early stages of HIV infection in T-cells. EMBO J. 1994 Dec 1;13(23):5559–5569. doi: 10.1002/j.1460-2075.1994.tb06893.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Benkirane M., Schmid-Antomarchi H., Littman D. R., Hirn M., Rossi B., Devaux C. The cytoplasmic tail of CD4 is required for inhibition of human immunodeficiency virus type 1 replication by antibodies that bind to the immunoglobulin CDR3-like region in domain 1 of CD4. J Virol. 1995 Nov;69(11):6904–6910. doi: 10.1128/jvi.69.11.6904-6910.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bernier R., Tremblay M. Homologous interference resulting from the presence of defective particles of human immunodeficiency virus type 1. J Virol. 1995 Jan;69(1):291–300. doi: 10.1128/jvi.69.1.291-300.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Boulerice F., Bour S., Geleziunas R., Lvovich A., Wainberg M. A. High frequency of isolation of defective human immunodeficiency virus type 1 and heterogeneity of viral gene expression in clones of infected U-937 cells. J Virol. 1990 Apr;64(4):1745–1755. doi: 10.1128/jvi.64.4.1745-1755.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Burkly L. C., Olson D., Shapiro R., Winkler G., Rosa J. J., Thomas D. W., Williams C., Chisholm P. Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced cell fusion. J Immunol. 1992 Sep 1;149(5):1779–1787. [PubMed] [Google Scholar]
  11. Caputo A., Sodroski J. G., Haseltine W. A. Constitutive expression of HIV-1 tat protein in human Jurkat T cells using a BK virus vector. J Acquir Immune Defic Syndr. 1990;3(4):372–379. [PubMed] [Google Scholar]
  12. Cefai D., Ferrer M., Serpente N., Idziorek T., Dautry-Varsat A., Debre P., Bismuth G. Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation. J Immunol. 1992 Jul 1;149(1):285–294. [PubMed] [Google Scholar]
  13. Chirmule N., Kalyanaraman V. S., Oyaizu N., Slade H. B., Pahwa S. Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. Blood. 1990 Jan 1;75(1):152–159. [PubMed] [Google Scholar]
  14. Corbeau P., Benkirane M., Weil R., David C., Emiliani S., Olive D., Mawas C., Serre A., Devaux C. Ig CDR3-like region of the CD4 molecule is involved in HIV-induced syncytia formation but not in viral entry. J Immunol. 1993 Jan 1;150(1):290–301. [PubMed] [Google Scholar]
  15. Cruikshank W. W., Center D. M., Pyle S. W., Kornfeld H. Biologic activities of HIV-1 envelope glycoprotein: the effects of crosslinking. Biomed Pharmacother. 1990;44(1):5–11. doi: 10.1016/0753-3322(90)90062-e. [DOI] [PubMed] [Google Scholar]
  16. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  17. Diamond D. C., Sleckman B. P., Gregory T., Lasky L. A., Greenstein J. L., Burakoff S. J. Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. J Immunol. 1988 Dec 1;141(11):3715–3717. [PubMed] [Google Scholar]
  18. Doyle C., Strominger J. L. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987 Nov 19;330(6145):256–259. doi: 10.1038/330256a0. [DOI] [PubMed] [Google Scholar]
  19. Eichmann K., Jönsson J. I., Falk I., Emmrich F. Effective activation of resting mouse T lymphocytes by cross-linking submitogenic concentrations of the T cell antigen receptor with either Lyt-2 or L3T4. Eur J Immunol. 1987 May;17(5):643–650. doi: 10.1002/eji.1830170510. [DOI] [PubMed] [Google Scholar]
  20. Emmrich F., Kanz L., Eichmann K. Cross-linking of the T cell receptor complex with the subset-specific differentiation antigen stimulates interleukin 2 receptor expression in human CD4 and CD8 T cells. Eur J Immunol. 1987 Apr;17(4):529–534. doi: 10.1002/eji.1830170415. [DOI] [PubMed] [Google Scholar]
  21. Fields A. P., Bednarik D. P., Hess A., May W. S. Human immunodeficiency virus induces phosphorylation of its cell surface receptor. Nature. 1988 May 19;333(6170):278–280. doi: 10.1038/333278a0. [DOI] [PubMed] [Google Scholar]
  22. Folks T., Powell D. M., Lightfoote M. M., Benn S., Martin M. A., Fauci A. S. Induction of HTLV-III/LAV from a nonvirus-producing T-cell line: implications for latency. Science. 1986 Feb 7;231(4738):600–602. doi: 10.1126/science.3003906. [DOI] [PubMed] [Google Scholar]
  23. Gay D., Maddon P., Sekaly R., Talle M. A., Godfrey M., Long E., Goldstein G., Chess L., Axel R., Kappler J. Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen. Nature. 1987 Aug 13;328(6131):626–629. doi: 10.1038/328626a0. [DOI] [PubMed] [Google Scholar]
  24. Gaynor R. Cellular transcription factors involved in the regulation of HIV-1 gene expression. AIDS. 1992 Apr;6(4):347–363. doi: 10.1097/00002030-199204000-00001. [DOI] [PubMed] [Google Scholar]
  25. Gelderblom H. R. Assembly and morphology of HIV: potential effect of structure on viral function. AIDS. 1991 Jun;5(6):617–637. [PubMed] [Google Scholar]
  26. Gelderblom H. R., Reupke H., Pauli G. Loss of envelope antigens of HTLV-III/LAV, a factor in AIDS pathogenesis? Lancet. 1985 Nov 2;2(8462):1016–1017. doi: 10.1016/s0140-6736(85)90570-7. [DOI] [PubMed] [Google Scholar]
  27. Goldman F., Jensen W. A., Johnson G. L., Heasley L., Cambier J. C. gp120 ligation of CD4 induces p56lck activation and TCR desensitization independent of TCR tyrosine phosphorylation. J Immunol. 1994 Oct 1;153(7):2905–2917. [PubMed] [Google Scholar]
  28. Goodenow M., Huet T., Saurin W., Kwok S., Sninsky J., Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed] [Google Scholar]
  29. Haffar O. K., Moran P. A., Smithgall M. D., Diegel M. L., Sridhar P., Ledbetter J. A., Zarling J. M., Hu S. L. Inhibition of virus production in peripheral blood mononuclear cells from human immunodeficiency virus (HIV) type 1-seropositive donors by treatment with recombinant HIV-like particles. J Virol. 1992 Jul;66(7):4279–4287. doi: 10.1128/jvi.66.7.4279-4287.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Hasunuma T., Tsubota H., Watanabe M., Chen Z. W., Lord C. I., Burkly L. C., Daley J. F., Letvin N. L. Regions of the CD4 molecule not involved in virus binding or syncytia formation are required for HIV-1 infection of lymphocytes. J Immunol. 1992 Mar 15;148(6):1841–1846. [PubMed] [Google Scholar]
  32. Hivroz C., Mazerolles F., Soula M., Fagard R., Graton S., Meloche S., Sekaly R. P., Fischer A. Human immunodeficiency virus gp120 and derived peptides activate protein tyrosine kinase p56lck in human CD4 T lymphocytes. Eur J Immunol. 1993 Mar;23(3):600–607. doi: 10.1002/eji.1830230303. [DOI] [PubMed] [Google Scholar]
  33. Horak I. D., Popovic M., Horak E. M., Lucas P. J., Gress R. E., June C. H., Bolen J. B. No T-cell tyrosine protein kinase signalling or calcium mobilization after CD4 association with HIV-1 or HIV-1 gp120. Nature. 1990 Dec 6;348(6301):557–560. doi: 10.1038/348557a0. [DOI] [PubMed] [Google Scholar]
  34. Jabado N., Le Deist F., Fisher A., Hivroz C. Interaction of HIV gp120 and anti-CD4 antibodies with the CD4 molecule on human CD4+ T cells inhibits the binding activity of NF-AT, NF-kappa B and AP-1, three nuclear factors regulating interleukin-2 gene enhancer activity. Eur J Immunol. 1994 Nov;24(11):2646–2652. doi: 10.1002/eji.1830241112. [DOI] [PubMed] [Google Scholar]
  35. Janeway C. A., Jr The role of CD4 in T-cell activation: accessory molecule or co-receptor? Immunol Today. 1989 Jul;10(7):234–238. doi: 10.1016/0167-5699(89)90260-0. [DOI] [PubMed] [Google Scholar]
  36. Julius M., Newell K., Maroun C., Haughn L. Functional consequences of CD4-TCR/CD3 interactions. Semin Immunol. 1991 May;3(3):161–166. [PubMed] [Google Scholar]
  37. Juszczak R. J., Turchin H., Truneh A., Culp J., Kassis S. Effect of human immunodeficiency virus gp120 glycoprotein on the association of the protein tyrosine kinase p56lck with CD4 in human T lymphocytes. J Biol Chem. 1991 Jun 15;266(17):11176–11183. [PubMed] [Google Scholar]
  38. Kaufmann R., Laroche D., Buchner K., Hucho F., Rudd C., Lindschau C., Ludwig P., Höer A., Oberdisse E., Kopp J. The HIV-1 surface protein gp120 has no effect on transmembrane signal transduction in T cells. J Acquir Immune Defic Syndr. 1992;5(8):760–770. [PubMed] [Google Scholar]
  39. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  40. Koga Y., Oh-Hori N., Sato H., Yamamoto N., Kimura G., Nomoto K. Absence of transcription of lck (lymphocyte specific protein tyrosine kinase) message in IL-2-independent, HTLV-I-transformed T cell lines. J Immunol. 1989 Jun 15;142(12):4493–4499. [PubMed] [Google Scholar]
  41. Kornfeld H., Cruikshank W. W., Pyle S. W., Berman J. S., Center D. M. Lymphocyte activation by HIV-1 envelope glycoprotein. Nature. 1988 Sep 29;335(6189):445–448. doi: 10.1038/335445a0. [DOI] [PubMed] [Google Scholar]
  42. Kupfer A., Singer S. J., Janeway C. A., Jr, Swain S. L. Coclustering of CD4 (L3T4) molecule with the T-cell receptor is induced by specific direct interaction of helper T cells and antigen-presenting cells. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5888–5892. doi: 10.1073/pnas.84.16.5888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lasky L. A., Nakamura G., Smith D. H., Fennie C., Shimasaki C., Patzer E., Berman P., Gregory T., Capon D. J. Delineation of a region of the human immunodeficiency virus type 1 gp120 glycoprotein critical for interaction with the CD4 receptor. Cell. 1987 Sep 11;50(6):975–985. doi: 10.1016/0092-8674(87)90524-1. [DOI] [PubMed] [Google Scholar]
  44. Ledbetter J. A., Gilliland L. K., Schieven G. L. The interaction of CD4 with CD3/Ti regulates tyrosine phosphorylation of substrates during T cell activation. Semin Immunol. 1990 Mar;2(2):99–106. [PubMed] [Google Scholar]
  45. Ledbetter J. A., June C. H., Grosmaire L. S., Rabinovitch P. S. Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1384–1388. doi: 10.1073/pnas.84.5.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Lenardo M. J., Baltimore D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989 Jul 28;58(2):227–229. doi: 10.1016/0092-8674(89)90833-7. [DOI] [PubMed] [Google Scholar]
  47. Li Y., Kappes J. C., Conway J. A., Price R. W., Shaw G. M., Hahn B. H. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. J Virol. 1991 Aug;65(8):3973–3985. doi: 10.1128/jvi.65.8.3973-3985.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Linette G. P., Hartzman R. J., Ledbetter J. A., June C. H. HIV-1-infected T cells show a selective signaling defect after perturbation of CD3/antigen receptor. Science. 1988 Jul 29;241(4865):573–576. doi: 10.1126/science.2899908. [DOI] [PubMed] [Google Scholar]
  49. Luo K. X., Sefton B. M. Cross-linking of T-cell surface molecules CD4 and CD8 stimulates phosphorylation of the lck tyrosine protein kinase at the autophosphorylation site. Mol Cell Biol. 1990 Oct;10(10):5305–5313. doi: 10.1128/mcb.10.10.5305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Mann D. L., Lasane F., Popovic M., Arthur L. O., Robey W. G., Blattner W. A., Newman M. J. HTLV-III large envelope protein (gp120) suppresses PHA-induced lymphocyte blastogenesis. J Immunol. 1987 Apr 15;138(8):2640–2644. [PubMed] [Google Scholar]
  51. Marrack P., Endres R., Shimonkevitz R., Zlotnik A., Dialynas D., Fitch F., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  53. McDougal J. S., Nicholson J. K., Cross G. D., Cort S. P., Kennedy M. S., Mawle A. C. Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. J Immunol. 1986 Nov 1;137(9):2937–2944. [PubMed] [Google Scholar]
  54. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  55. Mittler R. S., Hoffmann M. K. Synergism between HIV gp120 and gp120-specific antibody in blocking human T cell activation. Science. 1989 Sep 22;245(4924):1380–1382. doi: 10.1126/science.2571187. [DOI] [PubMed] [Google Scholar]
  56. Moore J. P., McKeating J. A., Huang Y. X., Ashkenazi A., Ho D. D. Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates. J Virol. 1992 Jan;66(1):235–243. doi: 10.1128/jvi.66.1.235-243.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Moscicki R. A., Amento E. P., Krane S. M., Kurnick J. T., Colvin R. B. Modulation of surface antigens of a human monocyte cell line, U937, during incubation with T lymphocyte-conditioned medium: detection of T4 antigen and its presence on normal blood monocytes. J Immunol. 1983 Aug;131(2):743–748. [PubMed] [Google Scholar]
  58. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  59. Neudorf S. M., Jones M. M., McCarthy B. M., Harmony J. A., Choi E. M. The CD4 molecule transmits biochemical information important in the regulation of T lymphocyte activity. Cell Immunol. 1990 Feb;125(2):301–314. doi: 10.1016/0008-8749(90)90086-7. [DOI] [PubMed] [Google Scholar]
  60. Orloff G. M., Kennedy M. S., Dawson C., McDougal J. S. HIV-1 binding to CD4 T cells does not induce a Ca2+ influx or lead to activation of protein kinases. AIDS Res Hum Retroviruses. 1991 Jul;7(7):587–593. doi: 10.1089/aid.1991.7.587. [DOI] [PubMed] [Google Scholar]
  61. Oyaizu N., Chirmule N., Kalyanaraman V. S., Hall W. W., Pahwa R., Shuster M., Pahwa S. Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2379–2383. doi: 10.1073/pnas.87.6.2379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Oyaizu N., Chirmule N., Ohnishi Y., Kalyanaraman V. S., Pahwa S. Human immunodeficiency virus type 1 envelope glycoproteins gp120 and gp160 induce interleukin-6 production in CD4+ T-cell clones. J Virol. 1991 Nov;65(11):6277–6282. doi: 10.1128/jvi.65.11.6277-6282.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Peterson A., Seed B. Genetic analysis of monoclonal antibody and HIV binding sites on the human lymphocyte antigen CD4. Cell. 1988 Jul 1;54(1):65–72. doi: 10.1016/0092-8674(88)90180-8. [DOI] [PubMed] [Google Scholar]
  64. Piatak M., Jr, Saag M. S., Yang L. C., Clark S. J., Kappes J. C., Luk K. C., Hahn B. H., Shaw G. M., Lifson J. D. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993 Mar 19;259(5102):1749–1754. doi: 10.1126/science.8096089. [DOI] [PubMed] [Google Scholar]
  65. Reinherz E. L., Schlossman S. F. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. doi: 10.1016/0092-8674(80)90072-0. [DOI] [PubMed] [Google Scholar]
  66. Rosoff P. M., Burakoff S. J., Greenstein J. L. The role of the L3T4 molecule in mitogen and antigen-activated signal transduction. Cell. 1987 Jun 19;49(6):845–853. doi: 10.1016/0092-8674(87)90622-2. [DOI] [PubMed] [Google Scholar]
  67. Schwartz O., Virelizier J. L., Montagnier L., Hazan U. A microtransfection method using the luciferase-encoding reporter gene for the assay of human immunodeficiency virus LTR promoter activity. Gene. 1990 Apr 16;88(2):197–205. doi: 10.1016/0378-1119(90)90032-m. [DOI] [PubMed] [Google Scholar]
  68. Shaw A. S., Amrein K. E., Hammond C., Stern D. F., Sefton B. M., Rose J. K. The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain. Cell. 1989 Nov 17;59(4):627–636. doi: 10.1016/0092-8674(89)90008-1. [DOI] [PubMed] [Google Scholar]
  69. Sleckman B. P., Peterson A., Jones W. K., Foran J. A., Greenstein J. L., Seed B., Burakoff S. J. Expression and function of CD4 in a murine T-cell hybridoma. Nature. 1987 Jul 23;328(6128):351–353. doi: 10.1038/328351a0. [DOI] [PubMed] [Google Scholar]
  70. Smith S. D., Shatsky M., Cohen P. S., Warnke R., Link M. P., Glader B. E. Monoclonal antibody and enzymatic profiles of human malignant T-lymphoid cells and derived cell lines. Cancer Res. 1984 Dec;44(12 Pt 1):5657–5660. [PubMed] [Google Scholar]
  71. Sodroski J., Patarca R., Rosen C., Wong-Staal F., Haseltine W. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985 Jul 5;229(4708):74–77. doi: 10.1126/science.2990041. [DOI] [PubMed] [Google Scholar]
  72. Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
  73. Terhorst C., van Agthoven A., Reinherz E., Schlossman S. Biochemical analysis of human T lymphocyte differentiation antigens T4 and T5. Science. 1980 Jul 25;209(4455):520–521. doi: 10.1126/science.6967228. [DOI] [PubMed] [Google Scholar]
  74. Tite J. P., Sloan A., Janeway C. A., Jr The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal. J Mol Cell Immunol. 1986;2(4):179–190. [PubMed] [Google Scholar]
  75. Tong-Starkesen S. E., Luciw P. A., Peterlin B. M. Signaling through T lymphocyte surface proteins, TCR/CD3 and CD28, activates the HIV-1 long terminal repeat. J Immunol. 1989 Jan 15;142(2):702–707. [PubMed] [Google Scholar]
  76. Tremblay M., Meloche S., Gratton S., Wainberg M. A., Sékaly R. P. Association of p56lck with the cytoplasmic domain of CD4 modulates HIV-1 expression. EMBO J. 1994 Feb 15;13(4):774–783. doi: 10.1002/j.1460-2075.1994.tb06320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Tremblay M., Numazaki K., Li X. G., Gornitsky M., Hiscott J., Wainberg M. A. Resistance to infection by HIV-1 of peripheral blood mononuclear cells from HIV-1-infected patients is probably mediated by neutralizing antibodies. J Immunol. 1990 Nov 1;145(9):2896–2901. [PubMed] [Google Scholar]
  78. Turner J. M., Brodsky M. H., Irving B. A., Levin S. D., Perlmutter R. M., Littman D. R. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 1990 Mar 9;60(5):755–765. doi: 10.1016/0092-8674(90)90090-2. [DOI] [PubMed] [Google Scholar]
  79. Wahl L. M., Corcoran M. L., Pyle S. W., Arthur L. O., Harel-Bellan A., Farrar W. L. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. doi: 10.1073/pnas.86.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Wassmer P., Chan C., Lögdberg L., Shevach E. M. Role of the L3T4-antigen in T cell activation. II. Inhibition of T cell activation by monoclonal anti-L3T4 antibodies in the absence of accessory cells. J Immunol. 1985 Oct;135(4):2237–2242. [PubMed] [Google Scholar]
  81. Willard-Gallo K. E., Van de Keere F., Kettmann R. A specific defect in CD3 gamma-chain gene transcription results in loss of T-cell receptor/CD3 expression late after human immunodeficiency virus infection of a CD4+ T-cell line. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6713–6717. doi: 10.1073/pnas.87.17.6713. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES