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. 1987 Jul;84(14):4919–4923. doi: 10.1073/pnas.84.14.4919

Multiple sequence elements are required for regulation of human T-cell leukemia virus gene expression.

C A Rosen, R Park, J G Sodroski, W A Haseltine
PMCID: PMC305218  PMID: 3037527

Abstract

The U3 region of the long terminal repeat (LTR) of human T-cell leukemia virus type I (HTLV-I) contains sequences that respond to the trans-activating transcription (tat) factor encoded by the pX region of the provirus. Results presented here show that there are multiple tat-responsive sequences within the LTR and that a single 21-nucleotide sequence, which is repeated three times within the U3 region, is sufficient to determine the response to the trans-activator. This sequence is capable of conferring a tat-responsive phenotype upon the HTLV-I and simian virus 40 promoters, independent of orientation. Sequences required for efficient HTLV-I LTR-directed gene expression are also located 3' to the site of RNA initiation, within the R and U5 regions of the LTR.

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Selected References

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

  1. Aldovini A., De Rossi A., Feinberg M. B., Wong-Staal F., Franchini G. Molecular analysis of a deletion mutant provirus of type I human T-cell lymphotropic virus: evidence for a doubly spliced x-lor mRNA. Proc Natl Acad Sci U S A. 1986 Jan;83(1):38–42. doi: 10.1073/pnas.83.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen I. S., McLaughlin J., Golde D. W. Long terminal repeats of human T-cell leukaemia virus II genome determine target cell specificity. Nature. 1984 May 17;309(5965):276–279. doi: 10.1038/309276a0. [DOI] [PubMed] [Google Scholar]
  3. Derse D., Caradonna S. J., Casey J. W. Bovine leukemia virus long terminal repeat: a cell type-specific promoter. Science. 1985 Jan 18;227(4684):317–320. doi: 10.1126/science.2981431. [DOI] [PubMed] [Google Scholar]
  4. Derse D., Casey J. W. Two elements in the bovine leukemia virus long terminal repeat that regulate gene expression. Science. 1986 Mar 21;231(4744):1437–1440. doi: 10.1126/science.3006241. [DOI] [PubMed] [Google Scholar]
  5. Dynan W. S., Tjian R. Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell. 1983 Mar;32(3):669–680. doi: 10.1016/0092-8674(83)90053-3. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Fujisawa J., Seiki M., Kiyokawa T., Yoshida M. Functional activation of the long terminal repeat of human T-cell leukemia virus type I by a trans-acting factor. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2277–2281. doi: 10.1073/pnas.82.8.2277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Gallo R. C., Wong-Staal F. Retroviruses as etiologic agents of some animal and human leukemias and lymphomas and as tools for elucidating the molecular mechanism of leukemogenesis. Blood. 1982 Sep;60(3):545–557. [PubMed] [Google Scholar]
  10. Goh W. C., Sodroski J., Rosen C., Essex M., Haseltine W. A. Subcellular localization of the product of the long open reading frame of human T-cell leukemia virus type I. Science. 1985 Mar 8;227(4691):1227–1228. doi: 10.1126/science.2983419. [DOI] [PubMed] [Google Scholar]
  11. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haseltine W. A., Sodroski J., Patarca R., Briggs D., Perkins D., Wong-Staal F. Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region. Science. 1984 Jul 27;225(4660):419–421. doi: 10.1126/science.6330894. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Kiyokawa T., Seiki M., Iwashita S., Imagawa K., Shimizu F., Yoshida M. p27x-III and p21x-III, proteins encoded by the pX sequence of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8359–8363. doi: 10.1073/pnas.82.24.8359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Legerski R. J., Hodnett J. L., Gray H. B., Jr Extracellular nucleases of pseudomonas BAL 31. III. Use of the double-strand deoxyriboexonuclease activity as the basis of a convenient method for the mapping of fragments of DNA produced by cleavage with restriction enzymes. Nucleic Acids Res. 1978 May;5(5):1445–1464. doi: 10.1093/nar/5.5.1445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  18. Mulligan R. C., Berg P. Selection for animal cells that express the Escherichia coli gene coding for xanthine-guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2072–2076. doi: 10.1073/pnas.78.4.2072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Paskalis H., Felber B. K., Pavlakis G. N. Cis-acting sequences responsible for the transcriptional activation of human T-cell leukemia virus type I constitute a conditional enhancer. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6558–6562. doi: 10.1073/pnas.83.17.6558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  22. Rice N. R., Stephens R. M., Couez D., Deschamps J., Kettmann R., Burny A., Gilden R. V. The nucleotide sequence of the env gene and post-env region of bovine leukemia virus. Virology. 1984 Oct 15;138(1):82–93. doi: 10.1016/0042-6822(84)90149-1. [DOI] [PubMed] [Google Scholar]
  23. Rosen C. A., Sodroski J. G., Haseltine W. A. Location of cis-acting regulatory sequences in the human T-cell leukemia virus type I long terminal repeat. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6502–6506. doi: 10.1073/pnas.82.19.6502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rosen C. A., Sodroski J. G., Kettman R., Burny A., Haseltine W. A. Trans activation of the bovine leukemia virus long terminal repeat in BLV-infected cells. Science. 1985 Jan 18;227(4684):320–322. doi: 10.1126/science.2981432. [DOI] [PubMed] [Google Scholar]
  25. Rosen C. A., Sodroski J. G., Kettman R., Haseltine W. A. Activation of enhancer sequences in type II human T-cell leukemia virus and bovine leukemia virus long terminal repeats by virus-associated trans-acting regulatory factors. J Virol. 1986 Mar;57(3):738–744. doi: 10.1128/jvi.57.3.738-744.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Shimotohno K., Golde D. W., Miwa M., Sugimura T., Chen I. S. Nucleotide sequence analysis of the long terminal repeat of human T-cell leukemia virus type II. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1079–1083. doi: 10.1073/pnas.81.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shimotohno K., Takano M., Teruuchi T., Miwa M. Requirement of multiple copies of a 21-nucleotide sequence in the U3 regions of human T-cell leukemia virus type I and type II long terminal repeats for trans-acting activation of transcription. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8112–8116. doi: 10.1073/pnas.83.21.8112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shimotohno K., Wachsman W., Takahashi Y., Golde D. W., Miwa M., Sugimura T., Chen I. S. Nucleotide sequence of the 3' region of an infectious human T-cell leukemia virus type II genome. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6657–6661. doi: 10.1073/pnas.81.21.6657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Sodroski J., Trus M., Perkins D., Patarca R., Wong-Staal F., Gelmann E., Gallo R., Haseltine W. A. Repetitive structure in the long-terminal-repeat element of a type II human T-cell leukemia virus. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4617–4621. doi: 10.1073/pnas.81.15.4617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  34. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wachsman W., Shimotohno K., Clark S. C., Golde D. W., Chen I. S. Expression of the 3' terminal region of human T-cell leukemia viruses. Science. 1984 Oct 12;226(4671):177–179. doi: 10.1126/science.6091270. [DOI] [PubMed] [Google Scholar]
  36. Yoshida M., Miyoshi I., Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]

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