1887

Journal of General Virology header logo

Volume 74, Issue 12

Influence of the human immunodeficiency virus type 1 Tat protein on the proliferation and differentiation of PC12 rat pheochromocytoma cells Free

Abstract

Rat pheochromocytoma PC12 cells were permanently transfected with a plasmid vector, containing the gene of human immunodeficiency virus type 1 (HIV-1). Various clones were obtained showing the production of different levels of bioactive Tat protein (Tat) after transient contransfection with an HIV-1 long terminal repeat-chloramphenicol acetyltransferase reporter plasmid. Under conditions of serum starvation, -positive PC12 clones expressing high levels of Tat showed a significantly ( < 0.05) higher proliferation rate with respect to both mock-transfected PC12 cells and -positive PC12 cells expressing lower levels of Tat. Moreover, all -positive PC12 cell clones showed a partial morphological differentiation into sympathetic-like neurons, when seeded in low density (5 × 10 cells/cm) cultures. On the other hand, mock-transfected PC12 cells showed the round shaped morphology typical of untreated PC12 cells and displayed signs of neuronal differentiation only after treatment with 100 ng/ml of nerve growth factor. The addition of 5 µg/ml of anti-Tat monoclonal antibody to the culture medium of -positive PC12 cell clones almost completely blocked their increased proliferation rate ( < 0.05), but did not affect neuronal differentiation. A significant ( < 0.05) increase in cell proliferation was consistently observed in PC12 cells supplemented with low concentrations of Tat (5 to 25 ng/ml), whereas neuronal differentiation was hardly affected by exogenous Tat. Our data strongly suggest that Tat exerts a complex influence on the proliferation and differentiation of PC12 cells, and this might help in increasing understanding of the pathogenesis of the frequent neurological disorders observed in AIDS patients.

  • Received:
  • Accepted:
  • Published Online:
© Journal of General Virology 1993
Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-74-12-2587
1993-12-01
2024-12-08
Loading full text...

Full text loading...

/deliver/fulltext/jgv/74/12/JV0740122587.html?itemId=/content/journal/jgv/10.1099/0022-1317-74-12-2587&mimeType=html&fmt=ahah

References

  1. Brenneman D. E., Westbrook G. L., Fitzgerald S. P., Ennist D. L., Elkins K. L., Ruff M. R., Pert C. B. 1988; Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature, London 335:639–642
     [Google Scholar]
  2. Buonaguro L., Barillari G., Chang H. K., Bohan C. A., Kao V., Morgan R., Gallo R. C., Ensoli B. 1992; Effects of the human immunodeficiency virus type 1 tat protein on the expression of inflammatory cytokines. Journal of Virology 66:7159–7167
     [Google Scholar]
  3. Cullen B. R. 1986; Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell 46:973–982
     [Google Scholar]
  4. Ensoli B., Barillari G., Zaki Salahuddin S., Gallo R. C., Wong-Staal F. 1990; Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients. Nature, London 345:84–86
     [Google Scholar]
  5. Ensoli B., Buonaguro L., Barillari G., Fiorelli V., Gendelman R., Morgan R. A., Wingfield P., Gallo R. C. 1993; Release, uptake and effects of extracellular human immunodeficiency virus type 1 tat protein on cell growth and viral transactivation. Journal of Virology 67:277–287
     [Google Scholar]
  6. Frankel A. D., Pabo C. O. 1988; Cellular uptake of the Tat protein from human immunodeficiency virus. Cell 55:1189–1193
     [Google Scholar]
  7. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
     [Google Scholar]
  8. Greene L. A. 1978; Nerve growth factor prevents the death and stimulates neuronal differentiation of clonal PC12 pheochromo-cytoma cells in serum-free medium. Journal of Cell Biology 78:747–755
     [Google Scholar]
  9. Greene L. A., Tischler A. S. 1976; Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proceedings of the National Academy of Sciences, U,. S,. A 73:2424–2428
     [Google Scholar]
  10. Grossi M. P., Caputo A., Rimessi P., Chiccoli L., Balboni P. G., Barbanti-Brodano G. 1988; New BK virus episomal vector for complementary DNA expression in human cells. Archives of Virology 102:275–283
     [Google Scholar]
  11. Huff K. R., Guroff G. 1979; Nerve growth factor-induced reduction in epidermal growth factor responsiveness and epidermal growth factor receptors in PC12 cells: an aspect of cell differentiation. Biochemical and Biophysical Research Communications 89:175–180
     [Google Scholar]
  12. Kim S. J., Winokur T. S., Lee H. D., Danielpour D., Kim K. Y., Geiser A. G., Chen L. S., Sporn M. B., Roberts A. B., Jay G. 1991; Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene. Molecular and Cellular Biology 11:5222–5228
     [Google Scholar]
  13. Martelli A. M., Neri L. M., Gilmour R. S., Barker P. J., Huskisson N. S., Manzoli F. A., Cocco L. 1991; Temporal changes in intracellular distribution of protein kinase C in Swiss 3T3 cells during mitogenic stimulation with insulin-like growth factor I and bombesin: translocation to the nucleus follows rapid changes in nuclear polyphosphoinositides. Biochemical and Biophysical Research Communications 177:480–487
     [Google Scholar]
  14. Merrill J. E., Chen I. S. Y. 1991; HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB Journal 5:2391–2397
     [Google Scholar]
  15. Neri L. M., Mazzotti G., Capitani S., Maraldi N. M., Cinti C., Baldini N., Rana R., Martelli A. M. 1992; Nuclear matrix bound replicational sites detected in situ by 5-bromodeoxyuridine. Histochemistry 98:19–32
     [Google Scholar]
  16. Prince R. W., Brew B. J., Sidtis J. J., Rosenblum M., Scheck A. C., Cleary P. 1988; The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592
     [Google Scholar]
  17. Rezai A., Martinez-Maza O., Gaynor R., Kishimoto T., Hirano T., Mitsuyasu R. T., Miles S. A. 1991; HIV-tat increases IL-6 production by and proliferation of AIDS-KS derived cells. Proceedings of the Annual Meeting of the American Society of Clinical Oncology 10:A6
     [Google Scholar]
  18. Rosen C. A., Sodroski J. C., Haseltine W. A. 1985; The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell 41:813–823
     [Google Scholar]
  19. Rosen C. A., Sodroski J. G., Goh W. C., Dayton A. I., Lippke J., Haseltine W. A. 1986; Post-transcriptional regulation accounts for the trans-activation of human T-lymphotropic virus type III. Nature, London 319:555–559
     [Google Scholar]
  20. Rudkin B. B., Lazarovici P., Levi B. Z., Abe Y., Fuiita K., Guroff G. 1989; Cell cycle-specific action of nerve growth factor in PC12 cells: differentiation without proliferation. EMBO Journal 241:3319–3325
     [Google Scholar]
  21. Rydel R. E., Greene L. A. 1987; Acid and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. Journal of Neuroscience 7:3639–3653
     [Google Scholar]
  22. Sastry K. J., Reddy H. R., Pandita R., Tolpal K., Aggarwal B. B. 1990; HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line. Journal of Biological Chemistry 265:20091–20093
     [Google Scholar]
  23. Satoh T., Nakamura S., Taga T., Matsuda T., Hirano T., Kishimoto T., Kaziro Y. 1988; Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. Molecular and Cellular Biology 8:3546–3549
     [Google Scholar]
  24. Taylor J. P., Cupp C., Diaz A., Chowdhury M., Khalili K., Jimenez S. A., Amini S. 1992; Activation of expression of genes coding for extracellular matrix proteins in tat-producing glioblastoma cells. Proceedings of the National Academy of Sciences U,. S,. A 89:9617–9621
     [Google Scholar]
  25. Viscidi R. P., Mayur K., Lederman H. M., Frankel A. D. 1989; Inhibition of antigen-induced lymphocyte proliferation by tat protein from HIV-1. Science 246:1606–1608
     [Google Scholar]
  26. Wahl S. M., Allen J. B., McCartney-Francis N., Morganti-Kossman M. C., Kossman T., Ellingsworth L., Mai U. E. H., Mergenhagen S. E., Orenstein J. M. 1991; Macrophage- and astrocyte-derived transforming growth factor β as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. Journal of Experimental Medicine 173:981–991
     [Google Scholar]
  27. Weiser B., Peress N., La Neve D., Eilbott D. J., Seidman R., Burger H. 1990; Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proceedings of the National Academy of Sciences, U,. S,. A 87:3997–4001
     [Google Scholar]
  28. Wright C. M., Felber B. K., Paskalis H., Pavlakis G. N. 1986; Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science 234:988–992
     [Google Scholar]
  29. Zauli G., Davis B. R., Re M. C., Visani G., Furlini G., LaPlaca M. 1992; Tat protein stimulates production of transforming growth factor-β 1 by marrow macrophages: a potential mechanism for HIV-1 induced hematopoietic suppression. Blood 80:3036–3043
     [Google Scholar]
  30. Zauli G., Furlini G., Re M. C., Milani D., Capitani S., La Placa M. 1993; Human immunodeficiency virus type 1 (HIV-1) tat-protein stimulates the production of interleukin-6 (IL-6) by peripheral blood monocytes. Microbiologica 16:115–120
     [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-74-12-2587
Loading
Influence of the human immunodeficiency virus type 1 Tat protein on the proliferation and differentiation of PC12 rat pheochromocytoma cells
J. Gen. Virol. 74, 2587 (1993); https://doi.org/10.1099/0022-1317-74-12-2587
/content/journal/jgv/10.1099/0022-1317-74-12-2587
/content/journal/jgv/10.1099/0022-1317-74-12-2587
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error