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. 1996 Oct;70(10):6847–6855. doi: 10.1128/jvi.70.10.6847-6855.1996

The simian foamy virus type 1 transcriptional transactivator (Tas) binds and activates an enhancer element in the gag gene.

M Campbell 1, C Eng 1, P A Luciw 1
PMCID: PMC190732  PMID: 8794326

Abstract

Simian and human foamy viruses (SFV and HFV) encode a transcriptional transactivator, Tas, which governs the levels of viral transcripts initiated by both the promoter in the long terminal repeat (LTR) and the internal promoter (IP) located within the env gene of these viruses. Tas-responsive target elements,(TRE) LTR in the LTR and (TRE) IP in the env gene, are located 5' of the TATA box in both viral promoters and function as orientation- and position-independent enhancers. We have identified a strong Tas-responsive element, designated TRE (GP), near the 3' end of the gag gene and preceding the pol gene of SFV-1. In transient-expression assays with plasmids containing reporter genes, a 59-bp DNA fragment containing TRE (GP) (nucleotides 2224 to 2282) functioned as an enhancer element, dependent on Tas, in several cell types and in the context of a heterologous basal promoter. DNase footprinting revealed that the fusion protein glutathione S-transferase-Tas, purified from genetically engineered bacteria, interacts with about 40 hp (nucleotides 2237 to 2279) in the TRE (GP). A low degree of sequence homology was noted between TRE (GP) and TRE (IP). In virus-infected cells, novel transcripts with 5' ends immediately upstream from the reverse transcriptase translation frame (nucleotides 2611 to 5778) were identified. Upstream of the start site for these transcripts is a TATA box (nucleotides 2575 to 2579), which was required for transcription in transient-expression assays. Although a spliced mRNA initiated in the viral LTR is implicated in the synthesis of the HFV Pol polyprotein which encodes protease, reverse transcriptase, and integrase, it is possible that SFV-1 contains a promoter within the pol gene for initiating a reverse transcriptase transcript. Taken together, these studies define a novel Tas-responsive enhancer element, which binds the viral transactivator, and a potential promoter within the pol gene.

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Selected References

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  1. Arrigo S., Yun M., Beemon K. cis-acting regulatory elements within gag genes of avian retroviruses. Mol Cell Biol. 1987 Jan;7(1):388–397. doi: 10.1128/mcb.7.1.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boerkoel C. F., Kung H. J. Transcriptional interaction between retroviral long terminal repeats (LTRs): mechanism of 5' LTR suppression and 3' LTR promoter activation of c-myc in avian B-cell lymphomas. J Virol. 1992 Aug;66(8):4814–4823. doi: 10.1128/jvi.66.8.4814-4823.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell M., Renshaw-Gegg L., Renne R., Luciw P. A. Characterization of the internal promoter of simian foamy viruses. J Virol. 1994 Aug;68(8):4811–4820. doi: 10.1128/jvi.68.8.4811-4820.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carlberg K., Ryden T. A., Beemon K. Localization and footprinting of an enhancer within the avian sarcoma virus gag gene. J Virol. 1988 May;62(5):1617–1624. doi: 10.1128/jvi.62.5.1617-1624.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cullen B. R., Lomedico P. T., Ju G. Transcriptional interference in avian retroviruses--implications for the promoter insertion model of leukaemogenesis. Nature. 1984 Jan 19;307(5948):241–245. doi: 10.1038/307241a0. [DOI] [PubMed] [Google Scholar]
  6. Elliott J. F., Pohajdak B., Talbot D. J., Shaw J., Paetkau V. Phorbol diester-inducible, cyclosporine-suppressible transcription from a novel promoter within the mouse mammary tumor virus env gene. J Virol. 1988 Apr;62(4):1373–1380. doi: 10.1128/jvi.62.4.1373-1380.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Emerman M., Temin H. M. Comparison of promoter suppression in avian and murine retrovirus vectors. Nucleic Acids Res. 1986 Dec 9;14(23):9381–9396. doi: 10.1093/nar/14.23.9381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Emerman M., Temin H. M. Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell. 1984 Dec;39(3 Pt 2):449–467. [PubMed] [Google Scholar]
  9. Enssle J., Jordan I., Mauer B., Rethwilm A. Foamy virus reverse transcriptase is expressed independently from the Gag protein. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4137–4141. doi: 10.1073/pnas.93.9.4137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. He F., Blair W. S., Fukushima J., Cullen B. R. The human foamy virus Bel-1 transcription factor is a sequence-specific DNA binding protein. J Virol. 1996 Jun;70(6):3902–3908. doi: 10.1128/jvi.70.6.3902-3908.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Herman S. A., Coffin J. M. Differential transcription from the long terminal repeats of integrated avian leukosis virus DNA. J Virol. 1986 Nov;60(2):497–505. doi: 10.1128/jvi.60.2.497-505.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Klaver B., Berkhout B. Comparison of 5' and 3' long terminal repeat promoter function in human immunodeficiency virus. J Virol. 1994 Jun;68(6):3830–3840. doi: 10.1128/jvi.68.6.3830-3840.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kögel D., Aboud M., Flügel R. M. Mutational analysis of the reverse transcriptase and ribonuclease H domains of the human foamy virus. Nucleic Acids Res. 1995 Jul 25;23(14):2621–2625. doi: 10.1093/nar/23.14.2621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Loh T. P., Sievert L. L., Scott R. W. Negative regulation of retrovirus expression in embryonal carcinoma cells mediated by an intragenic domain. J Virol. 1988 Nov;62(11):4086–4095. doi: 10.1128/jvi.62.11.4086-4095.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Löchelt M., Aboud M., Flügel R. M. Increase in the basal transcriptional activity of the human foamy virus internal promoter by the homologous long terminal repeat promoter in cis. Nucleic Acids Res. 1993 Sep 11;21(18):4226–4230. doi: 10.1093/nar/21.18.4226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Löchelt M., Flügel R. M., Aboud M. The human foamy virus internal promoter directs the expression of the functional Bel 1 transactivator and Bet protein early after infection. J Virol. 1994 Feb;68(2):638–645. doi: 10.1128/jvi.68.2.638-645.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Löchelt M., Flügel R. M. The human foamy virus pol gene is expressed as a Pro-Pol polyprotein and not as a Gag-Pol fusion protein. J Virol. 1996 Feb;70(2):1033–1040. doi: 10.1128/jvi.70.2.1033-1040.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Löchelt M., Muranyi W., Flügel R. M. Human foamy virus genome possesses an internal, Bel-1-dependent and functional promoter. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7317–7321. doi: 10.1073/pnas.90.15.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Mergia A., Pratt-Lowe E., Shaw K. E., Renshaw-Gegg L. W., Luciw P. A. cis-acting regulatory regions in the long terminal repeat of simian foamy virus type 1. J Virol. 1992 Jan;66(1):251–257. doi: 10.1128/jvi.66.1.251-257.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mergia A., Shaw K. E., Lackner J. E., Luciw P. A. Relationship of the env genes and the endonuclease domain of the pol genes of simian foamy virus type 1 and human foamy virus. J Virol. 1990 Jan;64(1):406–410. doi: 10.1128/jvi.64.1.406-410.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mergia A., Shaw K. E., Pratt-Lowe E., Barry P. A., Luciw P. A. Identification of the simian foamy virus transcriptional transactivator gene (taf). J Virol. 1991 Jun;65(6):2903–2909. doi: 10.1128/jvi.65.6.2903-2909.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mergia A. Simian foamy virus type 1 contains a second promoter located at the 3' end of the env gene. Virology. 1994 Feb 15;199(1):219–222. doi: 10.1006/viro.1994.1114. [DOI] [PubMed] [Google Scholar]
  24. Miller C. L., Garner R., Paetkau V. An activation-dependent, T-lymphocyte-specific transcriptional activator in the mouse mammary tumor virus env gene. Mol Cell Biol. 1992 Jul;12(7):3262–3272. doi: 10.1128/mcb.12.7.3262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nordeen S. K., Green P. P., 3rd, Fowlkes D. M. A rapid, sensitive, and inexpensive assay for chloramphenicol acetyltransferase. DNA. 1987 Apr;6(2):173–178. doi: 10.1089/dna.1987.6.173. [DOI] [PubMed] [Google Scholar]
  26. Nosaka T., Ariumi Y., Sakurai M., Takeuchi R., Hatanaka M. Novel internal promoter/enhancer of HTLV-I for Tax expression. Nucleic Acids Res. 1993 Nov 11;21(22):5124–5129. doi: 10.1093/nar/21.22.5124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rethwilm A. Regulation of foamy virus gene expression. Curr Top Microbiol Immunol. 1995;193:1–24. doi: 10.1007/978-3-642-78929-8_1. [DOI] [PubMed] [Google Scholar]
  28. Van Lint C., Burny A., Verdin E. The intragenic enhancer of human immunodeficiency virus type 1 contains functional AP-1 binding sites. J Virol. 1991 Dec;65(12):7066–7072. doi: 10.1128/jvi.65.12.7066-7072.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Verdin E., Becker N., Bex F., Droogmans L., Burny A. Identification and characterization of an enhancer in the coding region of the genome of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4874–4878. doi: 10.1073/pnas.87.12.4874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Verdin E., Van Lint C. Internal transcriptional regulatory elements in HIV-1 and other retroviruses. Cell Mol Biol (Noisy-le-grand) 1995 May;41(3):365–369. [PubMed] [Google Scholar]
  31. Yu S. F., Baldwin D. N., Gwynn S. R., Yendapalli S., Linial M. L. Human foamy virus replication: a pathway distinct from that of retroviruses and hepadnaviruses. Science. 1996 Mar 15;271(5255):1579–1582. doi: 10.1126/science.271.5255.1579. [DOI] [PubMed] [Google Scholar]
  32. Zou J. X., Luciw P. A. The transcriptional transactivator of simian foamy virus 1 binds to a DNA target element in the viral internal promoter. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):326–330. doi: 10.1073/pnas.93.1.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. el Kharroubi A., Verdin E. Protein-DNA interactions within DNase I-hypersensitive sites located downstream of the HIV-1 promoter. J Biol Chem. 1994 Aug 5;269(31):19916–19924. [PubMed] [Google Scholar]

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