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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1988 Nov;85(21):8291–8295. doi: 10.1073/pnas.85.21.8291

Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis.

K T Jeang 1, P R Shank 1, A Kumar 1
PMCID: PMC282415  PMID: 2847157

Abstract

The genomes of human retroviruses [human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus (HTLV-I)] encode positive trans-activator proteins, named tat. In the presence of tat, the transcriptional activity of the homologous HIV-1 or HTLV-I long terminal repeat (LTR) promoter is markedly increased. We have constructed mammalian cell lines that contain stably integrated copies of a HIV-1 or a HTLV-I LTR-chloramphenicol acetyltransferase (CAT) gene. When presynthesized HIV-1 or HTLV-I tat proteins were separately introduced into these cells in the presence of cycloheximide, we found a strong increase in the steady-state expression of the homologous viral LTR. Nuclear "run-on" assays verified that this tat-mediated enhancement, occurring in the absence of de novo cellular protein synthesis, was due to increased transcriptional initiation at the LTR promoter. We conclude that one aspect of transcriptional trans-activation of viral LTR by the HIV-1 and HTLV-I tat proteins does not require the production of new cellular proteins.

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Selected References

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  1. Altman R., Harrich D., Garcia J. A., Gaynor R. B. Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns. J Virol. 1988 Apr;62(4):1339–1346. doi: 10.1128/jvi.62.4.1339-1346.1988. [DOI] [PMC free article] [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. Barré-Sinoussi F., Chermann J. C., Rey F., Nugeyre M. T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vézinet-Brun F., Rouzioux C. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. doi: 10.1126/science.6189183. [DOI] [PubMed] [Google Scholar]
  4. Brady J., Jeang K. T., Duvall J., Khoury G. Identification of p40x-responsive regulatory sequences within the human T-cell leukemia virus type I long terminal repeat. J Virol. 1987 Jul;61(7):2175–2181. doi: 10.1128/jvi.61.7.2175-2181.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broder S., Gallo R. C. A pathogenic retrovirus (HTLV-III) linked to AIDS. N Engl J Med. 1984 Nov 15;311(20):1292–1297. doi: 10.1056/NEJM198411153112006. [DOI] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Cross S. L., Feinberg M. B., Wolf J. B., Holbrook N. J., Wong-Staal F., Leonard W. J. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cell. 1987 Apr 10;49(1):47–56. doi: 10.1016/0092-8674(87)90754-9. [DOI] [PubMed] [Google Scholar]
  8. Cullen B. R. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. doi: 10.1016/0092-8674(86)90696-3. [DOI] [PubMed] [Google Scholar]
  9. Feinberg M. B., Jarrett R. F., Aldovini A., Gallo R. C., Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986 Sep 12;46(6):807–817. doi: 10.1016/0092-8674(86)90062-0. [DOI] [PubMed] [Google Scholar]
  10. Felber B. K., Paskalis H., Kleinman-Ewing C., Wong-Staal F., Pavlakis G. N. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985 Aug 16;229(4714):675–679. doi: 10.1126/science.2992082. [DOI] [PubMed] [Google Scholar]
  11. Franza B. R., Jr, Josephs S. F., Gilman M. Z., Ryan W., Clarkson B. Characterization of cellular proteins recognizing the HIV enhancer using a microscale DNA-affinity precipitation assay. 1987 Nov 26-Dec 2Nature. 330(6146):391–395. doi: 10.1038/330391a0. [DOI] [PubMed] [Google Scholar]
  12. Fujisawa J., Seiki M., Sato M., Yoshida M. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. EMBO J. 1986 Apr;5(4):713–718. doi: 10.1002/j.1460-2075.1986.tb04272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gallo R. C. The first human retrovirus. Sci Am. 1986 Dec;255(6):88–98. doi: 10.1038/scientificamerican1286-88. [DOI] [PubMed] [Google Scholar]
  14. Garcia J. A., Wu F. K., Mitsuyasu R., Gaynor R. B. Interactions of cellular proteins involved in the transcriptional regulation of the human immunodeficiency virus. EMBO J. 1987 Dec 1;6(12):3761–3770. doi: 10.1002/j.1460-2075.1987.tb02711.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gendelman H. E., Phelps W., Feigenbaum L., Ostrove J. M., Adachi A., Howley P. M., Khoury G., Ginsberg H. S., Martin M. A. Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759–9763. doi: 10.1073/pnas.83.24.9759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hauber J., Perkins A., Heimer E. P., Cullen B. R. Trans-activation of human immunodeficiency virus gene expression is mediated by nuclear events. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6364–6368. doi: 10.1073/pnas.84.18.6364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Inoue J., Seiki M., Taniguchi T., Tsuru S., Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1. EMBO J. 1986 Nov;5(11):2883–2888. doi: 10.1002/j.1460-2075.1986.tb04583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jeang K. T., Giam C. Z., Nerenberg M., Khoury G. Abundant synthesis of functional human T-cell leukemia virus type I p40x protein in eucaryotic cells by using a baculovirus expression vector. J Virol. 1987 Mar;61(3):708–713. doi: 10.1128/jvi.61.3.708-713.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jeang K. T., Shank P. R., Rabson A. B., Kumar A. Synthesis of functional human immunodeficiency virus tat protein in baculovirus as determined by a cell-cell fusion assay. J Virol. 1988 Oct;62(10):3874–3878. doi: 10.1128/jvi.62.10.3874-3878.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  22. Kalyanaraman V. S., Sarngadharan M. G., Nakao Y., Ito Y., Aoki T., Gallo R. C. Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1653–1657. doi: 10.1073/pnas.79.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kao S. Y., Calman A. F., Luciw P. A., Peterlin B. M. Anti-termination of transcription within the long terminal repeat of HIV-1 by tat gene product. Nature. 1987 Dec 3;330(6147):489–493. doi: 10.1038/330489a0. [DOI] [PubMed] [Google Scholar]
  24. Kingston R. E., Baldwin A. S., Sharp P. A. Transcription control by oncogenes. Cell. 1985 May;41(1):3–5. doi: 10.1016/0092-8674(85)90049-2. [DOI] [PubMed] [Google Scholar]
  25. Lee T. H., Coligan J. E., Sodroski J. G., Haseltine W. A., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Essex M. Antigens encoded by the 3'-terminal region of human T-cell leukemia virus: evidence for a functional gene. Science. 1984 Oct 5;226(4670):57–61. doi: 10.1126/science.6089350. [DOI] [PubMed] [Google Scholar]
  26. Loeken M. R., Khoury G., Brady J. Stimulation of the adenovirus E2 promoter by simian virus 40 T antigen or E1A occurs by different mechanisms. Mol Cell Biol. 1986 Jun;6(6):2020–2026. doi: 10.1128/mcb.6.6.2020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  28. Peterlin B. M., Luciw P. A., Barr P. J., Walker M. D. Elevated levels of mRNA can account for the trans-activation of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9734–9738. doi: 10.1073/pnas.83.24.9734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rabson A. B., Martin M. A. Molecular organization of the AIDS retrovirus. Cell. 1985 Mar;40(3):477–480. doi: 10.1016/0092-8674(85)90189-8. [DOI] [PubMed] [Google Scholar]
  30. Reichel R., Kovesdi I., Nevins J. R. Activation of a preexisting cellular factor as a basis for adenovirus E1A-mediated transcription control. Proc Natl Acad Sci U S A. 1988 Jan;85(2):387–390. doi: 10.1073/pnas.85.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rice A. P., Mathews M. B. Transcriptional but not translational regulation of HIV-1 by the tat gene product. Nature. 1988 Apr 7;332(6164):551–553. doi: 10.1038/332551a0. [DOI] [PubMed] [Google Scholar]
  32. Rosen C. A., Sodroski J. G., Goh W. C., Dayton A. I., Lippke J., Haseltine W. A. Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III. Nature. 1986 Feb 13;319(6054):555–559. doi: 10.1038/319555a0. [DOI] [PubMed] [Google Scholar]
  33. Seigel L. J., Ratner L., Josephs S. F., Derse D., Feinberg M. B., Reyes G. R., O'Brien S. J., Wong-Staal F. Transactivation induced by human T-lymphotropic virus type III (HTLV III) maps to a viral sequence encoding 58 amino acids and lacks tissue specificity. Virology. 1986 Jan 15;148(1):226–231. doi: 10.1016/0042-6822(86)90419-8. [DOI] [PubMed] [Google Scholar]
  34. Seiki M., Hikikoshi A., Taniguchi T., Yoshida M. Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family. Science. 1985 Jun 28;228(4707):1532–1534. doi: 10.1126/science.2990031. [DOI] [PubMed] [Google Scholar]
  35. Seiki M., Inoue J., Takeda T., Yoshida M. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. EMBO J. 1986 Mar;5(3):561–565. doi: 10.1002/j.1460-2075.1986.tb04247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Slamon D. J., Shimotohno K., Cline M. J., Golde D. W., Chen I. S. Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science. 1984 Oct 5;226(4670):61–65. doi: 10.1126/science.6089351. [DOI] [PubMed] [Google Scholar]
  37. Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  38. Sodroski J., Rosen C., Wong-Staal F., Salahuddin S. Z., Popovic M., Arya S., Gallo R. C., Haseltine W. A. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985 Jan 11;227(4683):171–173. doi: 10.1126/science.2981427. [DOI] [PubMed] [Google Scholar]
  39. Wachsman W., Golde D. W., Temple P. A., Orr E. C., Clark S. C., Chen I. S. HTLV x-gene product: requirement for the env methionine initiation codon. Science. 1985 Jun 28;228(4707):1534–1537. doi: 10.1126/science.2990032. [DOI] [PubMed] [Google Scholar]

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