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. 1992 Jul;66(7):4617–4621. doi: 10.1128/jvi.66.7.4617-4621.1992

Human chromosome 12 is required for optimal interactions between Tat and TAR of human immunodeficiency virus type 1 in rodent cells.

A Alonso 1, D Derse 1, B M Peterlin 1
PMCID: PMC241279  PMID: 1602563

Abstract

Levels of trans activation of the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) by the virally encoded transactivator Tat show marked species-specific differences. For example, levels of transactivation observed in Chinese hamster ovary (CHO) rodent cells are 10-fold lower than those in human cells or in CHO cells that contain the human chromosome 12. Thus, the human chromosome 12 codes for a protein or proteins that are required for optimal Tat activity. Here, the function of these cellular proteins was analyzed by using a number of modified HIV-1 LTRs and Tats. Neither DNA-binding proteins that bind to the HIV-1 LTR nor proteins that interact with the activation domain of Tat could be implicated in this defect. However, since species-specific differences were no longer observed with hybrid proteins that contain the activation domain of Tat fused to heterologous RNA-binding proteins, optimal interactions between Tat and the trans-acting responsive RNA (TAR) must depend on this factor(s).

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Selected References

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  1. Barry P. A., Pratt-Lowe E., Peterlin B. M., Luciw P. A. Cytomegalovirus activates transcription directed by the long terminal repeat of human immunodeficiency virus type 1. J Virol. 1990 Jun;64(6):2932–2940. doi: 10.1128/jvi.64.6.2932-2940.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berkhout B., Gatignol A., Rabson A. B., Jeang K. T. TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. Cell. 1990 Aug 24;62(4):757–767. doi: 10.1016/0092-8674(90)90120-4. [DOI] [PubMed] [Google Scholar]
  3. Carroll R., Martarano L., Derse D. Identification of lentivirus tat functional domains through generation of equine infectious anemia virus/human immunodeficiency virus type 1 tat gene chimeras. J Virol. 1991 Jul;65(7):3460–3467. doi: 10.1128/jvi.65.7.3460-3467.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carroll R., Peterlin B. M., Derse D. Inhibition of human immunodeficiency virus type 1 Tat activity by coexpression of heterologous trans activators. J Virol. 1992 Apr;66(4):2000–2007. doi: 10.1128/jvi.66.4.2000-2007.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Celada A., Maki R. A. DNA binding of the mouse class II major histocompatibility CCAAT factor depends on two components. Mol Cell Biol. 1989 Jul;9(7):3097–3100. doi: 10.1128/mcb.9.7.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Derse D., Carvalho M., Carroll R., Peterlin B. M. A minimal lentivirus Tat. J Virol. 1991 Dec;65(12):7012–7015. doi: 10.1128/jvi.65.12.7012-7015.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dingwall C., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A. HIV-1 tat protein stimulates transcription by binding to a U-rich bulge in the stem of the TAR RNA structure. EMBO J. 1990 Dec;9(12):4145–4153. doi: 10.1002/j.1460-2075.1990.tb07637.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dingwall C., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A., Valerio R. Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6925–6929. doi: 10.1073/pnas.86.18.6925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dorn P., DaSilva L., Martarano L., Derse D. Equine infectious anemia virus tat: insights into the structure, function, and evolution of lentivirus trans-activator proteins. J Virol. 1990 Apr;64(4):1616–1624. doi: 10.1128/jvi.64.4.1616-1624.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Elangovan B., Subramanian T., Chinnadurai G. Functional comparison of the basic domains of the Tat proteins of human immunodeficiency virus types 1 and 2 in trans activation. J Virol. 1992 Apr;66(4):2031–2036. doi: 10.1128/jvi.66.4.2031-2036.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Endo S., Kubota S., Siomi H., Adachi A., Oroszlan S., Maki M., Hatanaka M. A region of basic amino-acid cluster in HIV-1 Tat protein is essential for trans-acting activity and nucleolar localization. Virus Genes. 1989 Nov;3(2):99–110. doi: 10.1007/BF00125123. [DOI] [PubMed] [Google Scholar]
  12. Feinberg M. B., Baltimore D., Frankel A. D. The role of Tat in the human immunodeficiency virus life cycle indicates a primary effect on transcriptional elongation. Proc Natl Acad Sci U S A. 1991 May 1;88(9):4045–4049. doi: 10.1073/pnas.88.9.4045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feng S., Holland E. C. HIV-1 tat trans-activation requires the loop sequence within tar. Nature. 1988 Jul 14;334(6178):165–167. doi: 10.1038/334165a0. [DOI] [PubMed] [Google Scholar]
  14. Garcia J. A., Harrich D., Pearson L., Mitsuyasu R., Gaynor R. B. Functional domains required for tat-induced transcriptional activation of the HIV-1 long terminal repeat. EMBO J. 1988 Oct;7(10):3143–3147. doi: 10.1002/j.1460-2075.1988.tb03181.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Garcia J. A., Harrich D., Soultanakis E., Wu F., Mitsuyasu R., Gaynor R. B. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation. EMBO J. 1989 Mar;8(3):765–778. doi: 10.1002/j.1460-2075.1989.tb03437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Harrich D., Garcia J., Wu F., Mitsuyasu R., Gonazalez J., Gaynor R. Role of SP1-binding domains in in vivo transcriptional regulation of the human immunodeficiency virus type 1 long terminal repeat. J Virol. 1989 Jun;63(6):2585–2591. doi: 10.1128/jvi.63.6.2585-2591.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hart C. E., Ou C. Y., Galphin J. C., Moore J., Bacheler L. T., Wasmuth J. J., Petteway S. R., Jr, Schochetman G. Human chromosome 12 is required for elevated HIV-1 expression in human-hamster hybrid cells. Science. 1989 Oct 27;246(4929):488–491. doi: 10.1126/science.2683071. [DOI] [PubMed] [Google Scholar]
  19. Hart C. E., Westhafer M. A., Galphin J. C., Ou C. Y., Bacheler L. T., Petteway S. R., Jr, Wasmuth J. J., Chen I. S., Schochetman G. Human chromosome-dependent and -independent pathways for HIV-2 trans-activation. AIDS Res Hum Retroviruses. 1991 Nov;7(11):877–882. doi: 10.1089/aid.1991.7.877. [DOI] [PubMed] [Google Scholar]
  20. Hauber J., Malim M. H., Cullen B. R. Mutational analysis of the conserved basic domain of human immunodeficiency virus tat protein. J Virol. 1989 Mar;63(3):1181–1187. doi: 10.1128/jvi.63.3.1181-1187.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jakobovits A., Smith D. H., Jakobovits E. B., Capon D. J. A discrete element 3' of human immunodeficiency virus 1 (HIV-1) and HIV-2 mRNA initiation sites mediates transcriptional activation by an HIV trans activator. Mol Cell Biol. 1988 Jun;8(6):2555–2561. doi: 10.1128/mcb.8.6.2555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jessen T. H., Oubridge C., Teo C. H., Pritchard C., Nagai K. Identification of molecular contacts between the U1 A small nuclear ribonucleoprotein and U1 RNA. EMBO J. 1991 Nov;10(11):3447–3456. doi: 10.1002/j.1460-2075.1991.tb04909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Jones K. A., Luciw P. A., Duchange N. Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters. Genes Dev. 1988 Sep;2(9):1101–1114. doi: 10.1101/gad.2.9.1101. [DOI] [PubMed] [Google Scholar]
  25. Kamine J., Subramanian T., Chinnadurai G. Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8510–8514. doi: 10.1073/pnas.88.19.8510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Kuppuswamy M., Subramanian T., Srinivasan A., Chinnadurai G. Multiple functional domains of Tat, the trans-activator of HIV-1, defined by mutational analysis. Nucleic Acids Res. 1989 May 11;17(9):3551–3561. doi: 10.1093/nar/17.9.3551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Laspia M. F., Rice A. P., Mathews M. B. HIV-1 Tat protein increases transcriptional initiation and stabilizes elongation. Cell. 1989 Oct 20;59(2):283–292. doi: 10.1016/0092-8674(89)90290-0. [DOI] [PubMed] [Google Scholar]
  29. Laspia M. F., Rice A. P., Mathews M. B. Synergy between HIV-1 Tat and adenovirus E1A is principally due to stabilization of transcriptional elongation. Genes Dev. 1990 Dec;4(12B):2397–2408. doi: 10.1101/gad.4.12b.2397. [DOI] [PubMed] [Google Scholar]
  30. Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Marciniak R. A., Calnan B. J., Frankel A. D., Sharp P. A. HIV-1 Tat protein trans-activates transcription in vitro. Cell. 1990 Nov 16;63(4):791–802. doi: 10.1016/0092-8674(90)90145-5. [DOI] [PubMed] [Google Scholar]
  32. Muesing M. A., Smith D. H., Cabradilla C. D., Benton C. V., Lasky L. A., Capon D. J. Nucleic acid structure and expression of the human AIDS/lymphadenopathy retrovirus. Nature. 1985 Feb 7;313(6002):450–458. doi: 10.1038/313450a0. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Newstein M., Stanbridge E. J., Casey G., Shank P. R. Human chromosome 12 encodes a species-specific factor which increases human immunodeficiency virus type 1 tat-mediated trans activation in rodent cells. J Virol. 1990 Sep;64(9):4565–4567. doi: 10.1128/jvi.64.9.4565-4567.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nodwell J. R., Greenblatt J. The nut site of bacteriophage lambda is made of RNA and is bound by transcription antitermination factors on the surface of RNA polymerase. Genes Dev. 1991 Nov;5(11):2141–2151. doi: 10.1101/gad.5.11.2141. [DOI] [PubMed] [Google Scholar]
  37. Pavlakis G. N., Felber B. K. Regulation of expression of human immunodeficiency virus. New Biol. 1990 Jan;2(1):20–31. [PubMed] [Google Scholar]
  38. 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]
  39. Rappaport J., Lee S. J., Khalili K., Wong-Staal F. The acidic amino-terminal region of the HIV-1 Tat protein constitutes an essential activating domain. New Biol. 1989 Oct;1(1):101–110. [PubMed] [Google Scholar]
  40. Rice A. P., Carlotti F. Mutational analysis of the conserved cysteine-rich region of the human immunodeficiency virus type 1 Tat protein. J Virol. 1990 Apr;64(4):1864–1868. doi: 10.1128/jvi.64.4.1864-1868.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  42. Roy S., Delling U., Chen C. H., Rosen C. A., Sonenberg N. A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. Genes Dev. 1990 Aug;4(8):1365–1373. doi: 10.1101/gad.4.8.1365. [DOI] [PubMed] [Google Scholar]
  43. Roy S., Parkin N. T., Rosen C., Itovitch J., Sonenberg N. Structural requirements for trans activation of human immunodeficiency virus type 1 long terminal repeat-directed gene expression by tat: importance of base pairing, loop sequence, and bulges in the tat-responsive sequence. J Virol. 1990 Mar;64(3):1402–1406. doi: 10.1128/jvi.64.3.1402-1406.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Ruben S., Perkins A., Purcell R., Joung K., Sia R., Burghoff R., Haseltine W. A., Rosen C. A. Structural and functional characterization of human immunodeficiency virus tat protein. J Virol. 1989 Jan;63(1):1–8. doi: 10.1128/jvi.63.1.1-8.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sadaie M. R., Benter T., Wong-Staal F. Site-directed mutagenesis of two trans-regulatory genes (tat-III,trs) of HIV-1. Science. 1988 Feb 19;239(4842):910–913. doi: 10.1126/science.3277284. [DOI] [PubMed] [Google Scholar]
  46. Selby M. J., Bain E. S., Luciw P. A., Peterlin B. M. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 1989 Apr;3(4):547–558. doi: 10.1101/gad.3.4.547. [DOI] [PubMed] [Google Scholar]
  47. Selby M. J., Peterlin B. M. Trans-activation by HIV-1 Tat via a heterologous RNA binding protein. Cell. 1990 Aug 24;62(4):769–776. doi: 10.1016/0092-8674(90)90121-t. [DOI] [PubMed] [Google Scholar]
  48. Sharmeen L., Bass B., Sonenberg N., Weintraub H., Groudine M. Tat-dependent adenosine-to-inosine modification of wild-type transactivation response RNA. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8096–8100. doi: 10.1073/pnas.88.18.8096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sheline C. T., Milocco L. H., Jones K. A. Two distinct nuclear transcription factors recognize loop and bulge residues of the HIV-1 TAR RNA hairpin. Genes Dev. 1991 Dec;5(12B):2508–2520. doi: 10.1101/gad.5.12b.2508. [DOI] [PubMed] [Google Scholar]
  50. Sherman P. A., Basta P. V., Moore T. L., Brown A. M., Ting J. P. Class II box consensus sequences in the HLA-DR alpha gene: transcriptional function and interaction with nuclear proteins. Mol Cell Biol. 1989 Jan;9(1):50–56. doi: 10.1128/mcb.9.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Staudt L. M., Clerc R. G., Singh H., LeBowitz J. H., Sharp P. A., Baltimore D. Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science. 1988 Jul 29;241(4865):577–580. doi: 10.1126/science.3399892. [DOI] [PubMed] [Google Scholar]
  52. Subramanian T., Govindarajan R., Chinnadurai G. Heterologous basic domain substitutions in the HIV-1 Tat protein reveal an arginine-rich motif required for transactivation. EMBO J. 1991 Aug;10(8):2311–2318. doi: 10.1002/j.1460-2075.1991.tb07768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Thompson L. H., Carrano A. V., Sato K., Salazar E. P., White B. F., Stewart S. A., Minkler J. L., Siciliano M. J. Identification of nucleotide-excision-repair genes on human chromosomes 2 and 13 by functional complementation in hamster-human hybrids. Somat Cell Mol Genet. 1987 Sep;13(5):539–551. doi: 10.1007/BF01534495. [DOI] [PubMed] [Google Scholar]
  54. Varmus H. Retroviruses. Science. 1988 Jun 10;240(4858):1427–1435. doi: 10.1126/science.3287617. [DOI] [PubMed] [Google Scholar]
  55. Warburton D., Gersen S., Yu M. T., Jackson C., Handelin B., Housman D. Monochromosomal rodent-human hybrids from microcell fusion of human lymphoblastoid cells containing an inserted dominant selectable marker. Genomics. 1990 Feb;6(2):358–366. doi: 10.1016/0888-7543(90)90577-h. [DOI] [PubMed] [Google Scholar]
  56. Weeks K. M., Ampe C., Schultz S. C., Steitz T. A., Crothers D. M. Fragments of the HIV-1 Tat protein specifically bind TAR RNA. Science. 1990 Sep 14;249(4974):1281–1285. doi: 10.1126/science.2205002. [DOI] [PubMed] [Google Scholar]
  57. Wright C. M., Felber B. K., Paskalis H., Pavlakis G. N. Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science. 1986 Nov 21;234(4779):988–992. doi: 10.1126/science.3490693. [DOI] [PubMed] [Google Scholar]
  58. Wu F., Garcia J., Sigman D., Gaynor R. tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185. Genes Dev. 1991 Nov;5(11):2128–2140. doi: 10.1101/gad.5.11.2128. [DOI] [PubMed] [Google Scholar]

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