1887

Abstract

While Rep proteins are required for adeno-associated virus (AAV) replication, little is known about cellular proteins that interact with Rep. We demonstrate here that transcription-positive cofactor 4 (PC4, p15) fused to Gal4-activating domain interacted with both AAV-2 and AAV-3 Rep proteins fused to Gal4 DNA-binding domain, leading to reporter activation in the yeast two-hybrid system. In addition to its coactivating function, PC4 recently has been shown to be involved in replication of simian virus 40. To study a functional role for the PC4-Rep protein interaction, 293–31 cells were cotransfected with a PC4 expression plasmid and an infectious clone of AAV-3, followed by superinfection with helper adenovirus. A significantly increased number of AAV-3 genomes were rescued in PC4 transfected cells. Our results support a possible involvement of PC4 in AAV replication and may be used in efficient production of AAV vectors for gene therapy.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-79-9-2157
1998-09-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/79/9/9747724.html?itemId=/content/journal/jgv/10.1099/0022-1317-79-9-2157&mimeType=html&fmt=ahah

References

  1. Ashktorab H., Srivastava A. 1989; Identification of nuclear proteins that specifically interact with adeno-associated virus type 2 inverted terminal repeat hairpin DNA. Journal of Virology 63:3034–3039
    [Google Scholar]
  2. Atchison R. W., Casto B. C., Hammon W. M. 1965; Adenovirus-associated defective virus particles. Science 149:754–756
    [Google Scholar]
  3. Buller R. M., Janik J. E., Sebring E. D., Rose J. A. 1981; Herpes simplex virus types 1 and 2 completely help adenovirus-associated virus replication. Journal of Virology 40:241–247
    [Google Scholar]
  4. Chang L. S., Shi Y., Shenk T. 1989; Adeno-associated virus P5 promoter contains an adenovirus E1A-inducible element and a binding site for the major late transcription factor. Journal of Virology 63:3479–3488
    [Google Scholar]
  5. Chiorini J. A., Weitzman M. D., Owens R. A., Urcelay E., Safer B., Kotin R. M. 1994a; Biologically active Rep proteins of adeno-associated virus type 2 produced as fusion proteins in Escherichia coli . Journal of Virology 68:797–804
    [Google Scholar]
  6. Chiorini J. A., Wiener S. M., Owens R. A., Kyostio S. R., Kotin R. M., Safer B. 1994b; Sequence requirements for stable binding and function of Rep68 on the adeno-associated virus type 2 inverted terminal repeats. Journal of Virology 68:7448–57
    [Google Scholar]
  7. Chiorini J. A., Yang L., Liu Y., Safer B., Kotin M. R. 1997; Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles. Journal of Virology 71:6823–6833
    [Google Scholar]
  8. Ge H., Roeder R. G. 1994; Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell 78:513–523
    [Google Scholar]
  9. Ge H., Zhao Y., Chait B. T., Roeder R. G. 1994; Phosphorylation negatively regulates the function of coactivator PC4. Proceedings of the National Academy of Sciences, USA 91:12691–12695
    [Google Scholar]
  10. Gietz D., St.Jean A., Woods R. A., Schiestl R. H. 1992; Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Research 20:1425
    [Google Scholar]
  11. Hermonat P. L., Labow M. A., Wright R., Berns K. I., Muzyczka N. 1984; Genetics of adeno-associated virus: isolation and preliminary characterization of adeno-associated virus type 2 mutants. Journal of Virology 51:329–339
    [Google Scholar]
  12. Hoggan M. D., Blacklow N. R., Rowe W. P. 1966; Studies of small DNA viruses found in various adenovirus preparations : physical, biological, and immunological characteristics. Proceedings of the National Academy of Sciences, USA 55:1467–1474
    [Google Scholar]
  13. Horer M., Weger S., Butz K., Hoppe Seyler F., Geisen C., Kleinschmidt J. A. 1995; Mutational analysis of adeno-associated virus Rep protein-mediated inhibition of heterologous and homologous promoters. Journal of Virology 69:5485–5496
    [Google Scholar]
  14. Im D. S., Muzyczka N. 1989; Factors that bind to adeno-associated virus terminal repeats. Journal of Virology 63:3095–3104
    [Google Scholar]
  15. Im D. S., Muzyczka N. 1990; The AAV origin binding protein Rep68 is an ATP-dependent site-specific endonuclease with DNA helicase activity. Cell 61:447–457
    [Google Scholar]
  16. Kaiser K., Stelzer G., Meisterernst M. 1995; The coactivator p15 (PC4) initiates transcriptional activation during TFIIA-TFIID-promoter complex formation. EMBO Journal 14:3520–3527
    [Google Scholar]
  17. Kaplitt M. G., Leone P., Samulski R. J., Xiao X., Pfaff D. W., O’Malley K. L., During M. J. 1994; Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nature Genetics 8:148–154
    [Google Scholar]
  18. Kessler P. D., Podsakoff G. M., Chen X., McQuiston S. A., Colosi P. C., Matelis L. A., Kurtzman G. J., Byrne B. J. 1996; Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proceedings of the National Academy of Sciences, USA 93:14082–14087
    [Google Scholar]
  19. Kretzschmar M., Kaiser K., Lottspeich F., Meisterernst M. 1994; A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators. Cell 78:525–534
    [Google Scholar]
  20. Kyostio S. R., Wonderling R. S., Owens R. A. 1995; Negative regulation of the adeno-associated virus (AAV) P5 promoter involves both the P5 rep binding site and the consensus ATP-binding motif of the AAV Rep68 protein. Journal of Virology 69:6787–6796
    [Google Scholar]
  21. Labow M. A., Hermonat P. L., Berns K. I. 1986; Positive and negative autoregulation of the adeno-associated virus type 2 genome. Journal of Virology 60:251–258
    [Google Scholar]
  22. Laughlin C. A., Jones N., Carter B. J. 1982; Effect of deletions in adenovirus early region 1 genes upon replication of adeno-associated virus. Journal of Virology 41:868–876
    [Google Scholar]
  23. McCarty D. M., Christensen M., Muzyczka N. 1991; Sequences required for coordinate induction of adeno-associated virus p19 and p40 promoters by Rep protein. Journal of Virology 65:2936–2945
    [Google Scholar]
  24. Muramatsu S., Mizukami H., Young N. S., Brown K. E. 1996; Nucleotide sequencing and generation of an infectious clone of adeno- associated virus 3. Virology 221:208–217
    [Google Scholar]
  25. Ni T. H., Zhou X., McCarty D. M., Zolotukhin I., Muzyczka N. 1994; In vitro replication of adeno-associated virus DNA. Journal of Virology 68:1128–1138
    [Google Scholar]
  26. Pan Z. Q., Ge H., Amin A. A., Hurwitz J. 1996; Transcriptionpositive cofactor 4 forms complexes with HSSB (RPA) on single-stranded DNA and influences HSSB-dependent enzymatic synthesis of simian virus 40 DNA. Journal of Biological Chemistry 271:22111–22116
    [Google Scholar]
  27. Pereira D. J., McCarty D. M., Muzyczka N. 1997; The adeno- associated virus (AAV) Rep protein acts as both a repressor and an activator to regulate AAV transcription during a productive infection. Journal of Virology 71:1079–1088
    [Google Scholar]
  28. Pereira D. J., Muzyczka N. 1997; The cellular transcription factor SP1 and an unknown cellular protein are required to mediate Rep protein activation of the adeno-associated virus p19 promoter. Journal of Virology 71:1747–1756
    [Google Scholar]
  29. Rutledge E. A., Halbert C. L., Russell D. W. 1998; Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. Journal of Virology 72:309–319
    [Google Scholar]
  30. Shi Y., Seto E., Chang L. S., Shenk T. 1991; Transcriptional repression by YY1, a human GLI-Kruppel-related protein, and relief of repression by adenovirus ElA protein. Cell 67:377–388
    [Google Scholar]
  31. Srivastava A., Lusby E. W., Berns K. I. 1983; Nucleotide sequence and organization of the adeno-associated virus 2 genome. Journal of Virology 45:555–564
    [Google Scholar]
  32. Tratschin J. D., Miller I. L., Carter B. J. 1984; Genetic analysis of adeno-associated virus: properties of deletion mutants constructed in vitro and evidence for an adeno-associated virus replication function. Journal of Virology 51:611–619
    [Google Scholar]
  33. Ward P., Dean F. B., O’Donnell M. E., Berns K. I. 1998; Role of the adenovirus DNA-binding protein in vitro adeno-associated virus DNA replication. Journal of Virology 72:420–427
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-79-9-2157
Loading
/content/journal/jgv/10.1099/0022-1317-79-9-2157
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