1887

Abstract

In order to investigate the molecular mechanism of the reported negative effect of the Nef protein of human immunodeficiency virus type 1 (HIV-1) on the cellular transcription factors NF-κB and AP-1, human T cell lines (both populations and subclones) expressing the gene from HIV-1 clone pNL432 were constructed. Functional expression of the gene was confirmed by downregulation of CD4 and MHC class I proteins on the cell surface as measured by fluorescence-activated cell sorter analysis. However, contrary to previous reports, no significant difference was found in the induced level of NF-κB and AP-1 activity between and cell lines upon stimulation by phorbol 12-myristate 13-acetate and phytohaemagglutinin, as measured by transient transfection and electromobility shift assays. These data indicate that the Nef protein does not have a negative effect on the induction of NF-κB and AP-1.

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1999-11-01
2020-08-11
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References

  1. Alexander L., Du Z., Rosenzweig M., Jung J. U., Desrosiers R. C.. 1997; A role for natural simian immunodeficiency virus and human immunodeficiency virus type 1 nef alleles in lymphocyte activation. Journal of Virology71:6094–6099
    [Google Scholar]
  2. Allan J. S., Coligan J. E., Lee T. H., McLane M. F., Kanki P. J., Groopman J. E., Essex M.. 1985; A new HTLV-III/LAV encoded antigen detected by antibodies from AIDS patients. Science230:810–813
    [Google Scholar]
  3. Bandres J. C., Ratner L.. 1994; Human immunodeficiency virus type 1 Nef protein down-regulates transcription factors NF-kappa B and AP-1 in human T cells in vitro after T-cell receptor stimulation. Journal of Virology68:3243–3249
    [Google Scholar]
  4. Beaver B., Wong-Staal F.. 1989; Structure of simian immunodeficiency virus regulatory gene. Proceedings of the National Academy of Sciences USA86:4813–4817
    [Google Scholar]
  5. Brigino E., Haraguchi S., Koutsonikolis A., Cianciolo G. J., Owens U., Good R. A., Day N. K.. 1997; Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin- dependent phosphodiesterase signal transduction pathway. Proceedings of the National Academy of Sciences USA94:3178–3182
    [Google Scholar]
  6. Byun J., Kim S. H., Kim J. M., Yu S. S., Robbins P. D., Yim J., Kim S.. 1996; Analysis of the relative level of gene expression from different retroviral vectors used for gene therapy. Gene Therapy9:780–788
    [Google Scholar]
  7. Chowers M. Y., Spina C. A., Kwoh T. J., Fitch N. J. S., Richman D. D., Guatelli J. C.. 1994; Optimal infectivity in vitro of human immunodeficiency virus type 1 required an intact nef gene.Journal of. Virology68:2906–2914
    [Google Scholar]
  8. Deacon N. J., Tsykin A., Solomon A., Smith K., Ludford-Menting M., Hooker D. J., McPhee D. A., Greenway A. L., Ellett A., Chatfield C., Lawson V. A., Crowe S., Maerz A., Sonza S., Learmont J., Sullivan J. S., Cunningham A., Dwyer D., Dowton D., Mills J.. 1995; Genomic structure of an attenuated quasispecies of HIV-1 from a cohort of a blood transfusion donor and recipients. Science270:988–991
    [Google Scholar]
  9. de Ronde A., Klaver B., Keulen W., Smith L., Goudsmit J.. 1992; Natural HIV-1 Nef accelerates virus replication in primary human lymphocytes. Virology187:391–395
    [Google Scholar]
  10. Dignam J. D., Lebovitz R. M., Roeder R. G.. 1983; Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.Nucleic. Acids Research11:1475–1489
    [Google Scholar]
  11. Finer M. H., Dull T. J., Qin L., Farson D., Roberts M. R.. 1994; kat: a high- efficiency retroviral transduction system for primary human T lymphocytes. Blood83:43–50
    [Google Scholar]
  12. Franchini G., Robert-Guroff M.. 1986; Cytoplasmic localisation of the HTLV III 3′ orf in cultured T cells. Virology155:593–599
    [Google Scholar]
  13. Greene W. C.. 1991; The molecular biology of human immunodeficiency virus type 1 infection.. New England Journal of Medicine324:308–317
    [Google Scholar]
  14. Greenway A., Azad A., McPhee D.. 1995; Human immunodeficiency virus type 1 Nef protein inhibits activation pathways in peripheral blood mononuclear cells and T-cell lines.. Journal of Virology69:1842–1850
    [Google Scholar]
  15. Grosschedl R., Baltimore D.. 1985; Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell41:885–897
    [Google Scholar]
  16. Kaminchik J., Bashan N., Itach A., N S., Gorecki M., Panet A.. 1991; Genetic characterization of human immunodeficiency virus type 1 nef gene products translated in vitro and expressed in mammalian cells. Journal of Virology65:583–588
    [Google Scholar]
  17. Kekule A. S., Lauer U., Weiss L., Luber B., Hofschneider P. H.. 1993; Negative regulation of human c-fos expression by the retinoblastoma gene product.. Nature346:668–671
    [Google Scholar]
  18. Kestler H. W., Ringler D. J., Mori K., Panicali D. L., Sehgal P. K., Daniel M. D., Desrosiers R. C.. 1991; Importance of the nef gene for maintenance of high virus loads and for the development of AIDS.. Cell65:651–662
    [Google Scholar]
  19. Kim S., Ikeuchi K., Byrn R., Groopman J., Baltimore D.. 1989; Lack of negative influence on viral growth by the nef gene of human immunodeficiency virus type 1.. Proceedings of the National Academy of Sciences USA86:9544–9588
    [Google Scholar]
  20. Kim S., Yu S. S., Kim V. N.. 1996; Essential role of NF- κB in transactivation of the human immunodeficiency virus long terminal repeat by the human cytomegalovirus IE1 protein.. Journal of General Virology77:83–91
    [Google Scholar]
  21. Kim S. H., Yu S. S., Park J. S., Robbins P. D., An C. S., Kim S.. 1998; Construction of retroviral vectors with improved safety, gene expression, and versatility. Journal of Virology72:994–1004
    [Google Scholar]
  22. Kirchhoff F., Greenough T. C., Brettler D. B., Sullivan J. L., Desrosiers R. C.. 1995; Absence of intact nef sequences in a long-term survivor with non-progressive HIV-1 infection.. New England Journal of Medicine332:228–232
    [Google Scholar]
  23. Miller M. D., Warmerdam M. T., Gaston I., Green W. C., Feinberg M. B.. 1994; The human immunodeficiency virus type 1 nef gene product: a positive factor for viral infection and replication in primary lymphocytes and macrophages.. Journal of Experimental Medicine179:101–113
    [Google Scholar]
  24. Nabel G., Baltimore D.. 1987; An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature326:711–713
    [Google Scholar]
  25. Niederman T. M., Garcia J. V., Hastings W. R., Luria S., Ratner L.. 1992; Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.. Journal of Virology66:6213–6219
    [Google Scholar]
  26. Page K. A., van Schooten W. C., Feinberg M. B.. 1997; Human immunodeficiency virus type 1 Nef does not alter T-cell sensitivity to antigen-specific stimulation.. Journal of Virology71:3776–3787
    [Google Scholar]
  27. Robbins P. D., Horowitz J. M., Mulligan R. C.. 1990; Negative regulation of human c-fos expression by the retinoblastoma gene product.. Nature346:668–671
    [Google Scholar]
  28. Schwartz O., Arenzana-Seisdedos F., Heard J. M., Danos O.. 1992; Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein.. AIDS Research and Human Retroviruses8:545–551
    [Google Scholar]
  29. Shibata R., Miura T., Hayami M., Ogawa K., Sakai H., Kiyomasu T., Ishimoto A., Adachi A.. 1990; Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) genome in relation to HIV-1 and simian immunodeficiency virus SIVAGM.. Journal of Virology64:742–747
    [Google Scholar]
  30. Spina C. A., Kwoh T. J., Chowers M. Y., Guatelli J. C., Richman D. D.. 1994; The importance of Nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes.. Journal of Experimental Medicine179:115–123
    [Google Scholar]
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