1887

Abstract

Nuclear protein binding sites in the long terminal repeat (LTR) of feline immunodeficiency virus (FIV) were identified by the method of DNase I footprinting. Using nuclear protein extracts from a feline T lymphoma cell line, several discrete footprints were generated upstream of the transcriptional initiation site (−50 to −150). The specificity of protein binding was examined by competition with oligonucleotides representing consensus DNA binding sites for known transcription factors. Binding to AP-1 (−124) and ATF (−58) motifs was observed, with cross-competition between these sites. A strong footprint signal was also detected over a tandemly repeated C/EBP motif (−94, −86) and an adjacent weaker footprint was found to be specific for an NF1 motif (−72/ −63). The effect on FIV LTR promoter activity of progressively deleting these nuclear factor binding sites was examined by linking LTR deletion mutants to the chloramphenicol acetyltransferase (CAT) gene. Deletion of the AP-1 site caused a 10- to 25-fold loss of CAT activity whereas deletion past the ATP site reduced activity virtually to background levels. The effects of deleting the C/EBP and NF1 sites were less marked and varied according to cell type. Transactivation of the LTR was assayed using constructs linked to a CAT reporter gene. The full-length FIV LTR was not significantly trans-activated. However, the expression of a deleted LTR construct lacking the AP- 4/AP-l site but retaining C/EBP and ATF sites was partially restored by co-infection with FIV or by cotransfection with an infectious molecular clone of FIV (FIV-PPR). These results show that host transcription factors responsive to cellular activation have a major role in regulating FIV expression, and suggest that virus- coded trans-activators acting through U3 may play a role in some cellular environments.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-3-545
1994-03-01
2024-12-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/3/JV0750030545.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-3-545&mimeType=html&fmt=ahah

References

  1. Boral A. L., Okenquist S. A., Lenz J. 1989; Identification of the SL3-3 virus enhancer core as a T-lymphoma cell-specific element. Journal of Virology 63:76–84
    [Google Scholar]
  2. Carpenter S., Alexandersen S., Long M. J., Perryman S., Chesebro B. 1993; Identification of a hypervariable region in the long terminal repeat of equine infectious anemia virus. Journal of Virology 65:1605–1610
    [Google Scholar]
  3. Cullen B. R. 1991; Human immunodeficiency virus as a prototypic complex retrovirus. Journal of Virology 65:1053–1056
    [Google Scholar]
  4. Derse D., Dorn P. L., Levy L., Stephens R. M., Rice N. R., Casey J. W. 1987; Characterization of equine infectious anemia virus long terminal repeat. Journal of Virology 61:743–747
    [Google Scholar]
  5. Derse D., Carroll R., Carvalho M. 1993; Transcriptional regulation of equine infectious anemia virus. Seminars in Virology 4:53–60
    [Google Scholar]
  6. Dorn P., Dasilva L., Martarano L., Derse D. 1990; Equine infectious anemia virus tat: insights into the structure, function and evolution of lentivirus transactivator proteins. Journal of Virology 64:1616–1624
    [Google Scholar]
  7. Fischinger P. J., Peebles P. T., Nomura S., Haapala D. K. 1973; Isolation of RD-144-like oncornavirus from a cat cell line. Journal of Virology 11:978–985
    [Google Scholar]
  8. Fulton R., Plumb M., Shield L., Neil J. C. 1990; Structural diversity and nuclear protein binding sites in the long terminal repeats of feline leukemia virus. Journal of Virology 64:1675–1682
    [Google Scholar]
  9. Gabudza D. H., Hess J. L., Small J. A., Clements J. E. 1989; Regulation of the visna virus long terminal repeat in macrophages involves cellular factors that bind sequences containing AP-1 sites. Molecular and Cellular Biology 9:2728–2733
    [Google Scholar]
  10. Gey G. O., Coffman W. D., Kubicek M. T. 1952; Tissue culture studies of the proliferative capacity of cervical carcinoma of normal epithelium. Cancer Research 12:264–265
    [Google Scholar]
  11. Gorman C., 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]
  12. Graham F. L., Van Der Eb A. J. 1973; A new technique for the assay of infectivity of human adenovirus 5 DNA. Virologv 52:456–467
    [Google Scholar]
  13. Gronostajski R. M. 1986; Analysis of nuclear factor I binding to DNA using degenerate oligonucleotides. Nucleic Acids Research 14:9117–9132
    [Google Scholar]
  14. Hai T., Liu F., Allegretto E. A., Karin M., Green M. R. 1988; A family of immunologically related transcription factors that includes multiple forms of ATF and AP-1. Genes and Development 2:1216–1226
    [Google Scholar]
  15. Hess J. L., Small J. A., Clements J. E. 1989; Sequences in the visna virus long terminal repeat that control transcriptional activity and respond to viral trans-activation: involvement of AP-1 sites in basal activity and trans-activation. Journal of Virologv 63:3001–3015
    [Google Scholar]
  16. Hosie M. J., Jarrett O. 1990; Serological responses of cats to feline immunodeficiency virus. AIDS 4:215–220
    [Google Scholar]
  17. Hosie M. J., Robertson C., Jarrett O. 1989; Prevalence of feline leukaemia virus and antibodies to feline immunodeficiency virus in cats in the United Kingdom. Veterinary Record 125:293–297
    [Google Scholar]
  18. Hosie M. J., Willett B., Dunsford T., Jarrett O., Neil J. C. 1993; An antibody which binds to a 24 kd cell surface protein identifies a possible non-CD4 receptor for feline immunodeficiency virus. Journal of Virology 67:1667–1671
    [Google Scholar]
  19. Katoh I., Yoshinaka Y., Ikawa Y. 1989; Bovine leukemia virus trans-activator p38tax activates heterologous promoters with a common sequence known as cAMP-responsive element or the binding site of a cellular transcription factor ATF. EMBO Journal 8:497–503
    [Google Scholar]
  20. Kawaguchi Y., Norimine J., Kai C., Mikami T. 1992; Sequences within the feline immunodeficiency virus long terminal repeat that regulate gene expression and respond to activation by feline herpesvirus type 1. Virology 190:465–468
    [Google Scholar]
  21. Landschultz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. 1988; Isolation of a recombinant copy of the gene encoding C/EBP. Genes and Development 2:786–800
    [Google Scholar]
  22. Lee W., Haslinger A., Karin M., Tjian R. 1987; Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature; London: 325368–372
    [Google Scholar]
  23. Lin Y. -S., Green M. R. 1988; Interaction of a common cellular transcription factor, ATF, with regulatory elements in both Ela- and cyclic AMP-inducible promoters. Proceedings of the National Academy of Sciences, U.S.A 85:414–417
    [Google Scholar]
  24. Marsh J. L., Erfle M., Wykes E. J. 1984; The pIC plasmid and phage vectors with versatile cloning sites for recombinant selection by insertional inactivation. Gene 32:481–485
    [Google Scholar]
  25. Maxam A. M., Gilbert W. 1980; Sequencing end-labeled DNA with base-specific chemical cleavages. Methods in Emymology 65:499–560
    [Google Scholar]
  26. Mermod N., Williams T. J., Tjian R. 1988; Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature; London: 332557–561
    [Google Scholar]
  27. Miyazawa T., Fukasawa M., Hasegawa A., Maki N., Ikuta K., Takahashi E., Hayami M., Mikima T. 1991; Molecular cloning of a novel isolate of feline immunodeficiency virus biologically and genetically different from the original U.S. isolate. Journal of Virology 65:1572–1577
    [Google Scholar]
  28. Olmsted R. A., Barnes A. K., Yamamoto J. K., Hirsch V. M., Purcell R. H., Johnson P. R. 1989a; Molecular cloning of feline immunodeficiency virus. Proceedings of the National Academv of Sciences, U.S.A 86:2448–2452
    [Google Scholar]
  29. Olmsted R. A., Hirsch V. M., Purcell R. H., Johnson P. R. 1989b; Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to other lentiviruses. Proceedings of the National Academy of Sciences, U.S.A 86:8088–8092
    [Google Scholar]
  30. Ondek B., Gloss L., Herr W. 1988; The SV40 enhancer contains two distinct levels of organization. Nature; London: 333:40–45
    [Google Scholar]
  31. Pedersen N. C., Ho E. W., Brown M. L., Yamamoto J. K. 1987; Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 235:790–793
    [Google Scholar]
  32. Phillips T. R., Talbott R. L., Lamont C., Muir S., Lovelace K., Elder J. H. 1990; Comparison of two host cell range variants of feline immunodeficiency virus. Journal of Virology 64:4605–4613
    [Google Scholar]
  33. Piette J., Hirai S., Yaniv M. 1988; Constitutive synthesis of activator protein 1 transcription factor after viral transformation of mouse fibroblasts. Proceedings of the National Academy of Sciences, U.S.A 85:3401–3405
    [Google Scholar]
  34. Plumb M. A., Goodwin G. H. 1988; Detection of sequence-specific DNA-protein interactions by the DNA footprinting technique. In Methods in Molecular Biology pp. 139–164 Walker J. M. Edited by Clifton: Humana Press;
    [Google Scholar]
  35. Plumb M., Fulton R., Breimer L., Stewart M., Willison K., Neil J. C. 1991; Nuclear factor 1 activates the feline leukemia virus long terminal repeat but is post-transcriptionally down-regulated in leukemia cell lines. Journal of Virology 65:1991–1999
    [Google Scholar]
  36. Rasheed S., Gardner M. B. 1980; Characterization of cat cell cultures for expression of retrovirus, FOCMA and endogenous sarc genes. In Proceedings of the Third International Feline Leukemia Virus Meeting pp. 393–400 Essex M., McClelland A. J. Edited by Amsterdam: Elsevier/North-Holland;
    [Google Scholar]
  37. Rickard C. G., Post J. E., Denoronha F., Barry L. M. 1969; A transmissible virus-induced lymphocytic leukemia of the cat. Journal of the National Cancer Institute 42:987–1014
    [Google Scholar]
  38. Rigby M. A., Holmes E. C., Pistello M., Mackay A., LeighBrown A. J., Neil J. C. 1993; Evolution of structural proteins of feline immunodeficiency virus: molecular epidemiology and evidence of selection for change. Journal of General Virology 74:425–436
    [Google Scholar]
  39. Rosen C. A., Sodroski J. G., 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]
  40. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A 74:5463–5467
    [Google Scholar]
  41. Santoro C., Mermod N., Andrews P. C., Tjian R. 1988; A family of human CCAAT-box-binding proteins active in transcription and DNA replication: cloning and expression of multiple cDNAs. Nature; London: 334218–224
    [Google Scholar]
  42. Shaw J. P., Utz P. J., Durand D. B., Toule J. J., Emmel E. A., Crabtree G. R. 1988; Identification of a putative regulator of early T cell activation genes. Science 241:202–203
    [Google Scholar]
  43. Shih D. S., Carruth L. M., Anderson M., Clements J. E. 1992; Involvement of FOS and JUN in the activation of visna virus gene expression in macrophages through an AP-1 site in the viral LTR. Virology 190:84–91
    [Google Scholar]
  44. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. 1987; Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-1. Science 238:1575–1578
    [Google Scholar]
  45. Spandidos D. A., Riggio M. 1986; Promoter and enhancer like activity at the 5′ end of normal and T24 Ha-ras-1 genes. FEBS Letters 203:169–174
    [Google Scholar]
  46. Sparger E. E., Shacklett B. L., Renshaw-Gegg L., Barry P. A., Pedersen N. C., Luciw P. A. 1992; Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. Virology 187:165–177
    [Google Scholar]
  47. Speck N. A., Baltimore D. 1987; Six distinct nuclear factors interact with the 75-base-pair repeat of the Moloney leukemia virus enhancer. Molecular and Cellular Biology 7:1101–1110
    [Google Scholar]
  48. Talbott R. L., Sparger E. E., Lovelace K. M., Fitch W. M., Pedersen N. C., Luciw P. A., Elder J. H. 1989; Nucleotide sequence and genomic organization of feline immunodeficiency virus. Proceedings of the National Academy of Sciences, U.S.A 86:5743–5747
    [Google Scholar]
  49. Temin H. M. 1981; Structure, variation and synthesis of retrovirus long terminal repeat. Cell 27:1–3
    [Google Scholar]
  50. Thornell A., Halberg B., Grundstrom T. 1988; Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3-3. Molecular and Cellular Biology 8:1625–1637
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-75-3-545
Loading
/content/journal/jgv/10.1099/0022-1317-75-3-545
Loading

Data & Media loading...

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