1887

Abstract

Human adenovirus serotype 5 encodes three proteins, E1b 55K, E4 Orf3 and E4 Orf6, which interact with each other and with components of the nucleus to regulate mRNA processing and export, viral DNA replication and p53-dependent apoptosis. Previous studies have shown that, during wild-type infection, 55K associates initially with structures termed ND10, which are sites of localization of the promyelocytic leukaemia protein, and then moves, dependent upon its interaction with Orf6, to the establishing virus replication centres. Absence of either Orf3 or Orf6 affects the localization of 55K and so may affect its function. In this study, the influence of Orf3 and Orf6 expression on the association of 55K with the insoluble matrix fraction of the nucleus and with ND10 particularly was examined. Overexpression of Orf6 was sufficient to block the association of 55K with this fraction, irrespective of the presence of Orf3. This effect depended upon the two proteins being able to interact. However, the association of 55K with ND10, which persists throughout infection in the absence of Orf6, required Orf3 to be present, thus distinguishing two subsets of matrix-associated 55K. A modified form of 55K, formation of which was blocked by mutating the known site of SUMO-1 attachment, was more abundant in the absence of Orf6 but unaffected by the absence of Orf3. Thus, this modification is favoured when 55K remains associated with the matrix but does not correlate with its stable association with ND10, many components of which are modified by SUMO-1.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.18820-0
2003-02-01
2019-10-21
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/2/vir840259.html?itemId=/content/journal/jgv/10.1099/vir.0.18820-0&mimeType=html&fmt=ahah

References

  1. Bondesson, M., Öhman, K., Manervik, M., Fan, S. & Akusjärvi, G. ( 1996; ). Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter. J Virol 70, 3844–3851.
    [Google Scholar]
  2. Carvalho, T., Seeler, J. S., Öhman, K., Jordan, P., Pettersson, U., Akusjärvi, G., Carmo-Fonseca, M. & Dejean, A. ( 1995; ). Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies. J Cell Biol 131, 45–56.[CrossRef]
    [Google Scholar]
  3. Chelbi-Alix, M. K., Quignon, F., Pelicano, L., Koken, M. H. M. & de Thé, H. ( 1998; ). Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein. J Virol 72, 1043–1051.
    [Google Scholar]
  4. Cutt, J. R., Shenk, T. & Hearing, P. ( 1987; ). Analysis of adenovirus early region 4-encoded polypeptides synthesized in productively infected cells. J Virol 61, 543–552.
    [Google Scholar]
  5. Dix, I. & Leppard, K. N. ( 1993; ). Regulated splicing of adenovirus type 5 E4 transcripts and regulated cytoplasmic accumulation of E4 mRNA. J Virol 67, 3226–3231.
    [Google Scholar]
  6. Dix, I. & Leppard, K. N. ( 1995; ). Expression of adenovirus type 5 E4 Orf2 protein during lytic infection. J Gen Virol 76, 1051–1055.[CrossRef]
    [Google Scholar]
  7. Dobbelstein, M., Roth, J., Kimberly, W. T., Levine, A. J. & Shenk, T. ( 1997; ). Nuclear export of the E1B 55-kDa and E4 34-kDa adenoviral oncoproteins mediated by a rev-like signal sequence. EMBO J 16, 4276–4284.[CrossRef]
    [Google Scholar]
  8. Dobner, T., Horikoshi, N., Rubenwolf, S. & Shenk, T. ( 1996; ). Blockage by adenovirus E4orf6 of transcriptional activation by the p53 tumor suppressor. Science 272, 1470–1473.[CrossRef]
    [Google Scholar]
  9. Dosch, T., Horn, F., Schneider, G., Kratzer, F., Dobner, T., Hauber, J. & Stauber, R. H. ( 2001; ). The adenovirus type 5 E1B-55K oncoprotein actively shuttles in virus-infected cells, whereas transport of E4orf6 is mediated by a CRM1-independent mechanism. J Virol 75, 5677–5683.[CrossRef]
    [Google Scholar]
  10. Doucas, V., Ishov, A. M., Romo, A., Juguilon, H., Weitzman, M. D., Evans, R. M. & Maul, G. G. ( 1996; ). Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure. Genes Dev 10, 196–207.[CrossRef]
    [Google Scholar]
  11. Endter, C., Kzhyshkowska, J., Stauber, R. & Dobner, T. ( 2001; ). SUMO-1 modification required for transformation by adenovirus type 5 early region 1B 55-kDa oncoprotein. Proc Natl Acad Sci U S A 98, 11312–11317.[CrossRef]
    [Google Scholar]
  12. Everett, R. D. ( 2001; ). DNA viruses and viral proteins that interact with PML nuclear bodies. Oncogene 20, 7266–7273.[CrossRef]
    [Google Scholar]
  13. Gonzalez, R. A. & Flint, S. J. ( 2002; ). Effects of mutations in the adenoviral E1B 55-kilodalton protein coding sequence on viral late mRNA metabolism. J Virol 76, 4507–4519.[CrossRef]
    [Google Scholar]
  14. Goodrum, F. D., Shenk, T. & Ornelles, D. A. ( 1996; ). Adenovirus early region 4 34-kilodalton protein directs the nuclear localization of the early region 1B 55-kilodalton protein in primate cells. J Virol 70, 6323–6335.
    [Google Scholar]
  15. Halbert, D. N., Cutt, J. R. & Shenk, T. ( 1985; ). Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. J Virol 56, 250–257.
    [Google Scholar]
  16. Huang, M.-M. & Hearing, P. ( 1989; ). Adenovirus early region 4 encodes two gene products with redundant effects in lytic infection. J Virol 63, 2605–2615.
    [Google Scholar]
  17. Imperiale, M. J., Akusjärvi, G. & Leppard, K. N. ( 1995; ). Post-transcriptional control of adenovirus gene expression. Curr Top Microbiol Immunol 199, 139–171.
    [Google Scholar]
  18. Jones, N. C. & Shenk, T. ( 1978; ). Isolation of deletion and substitution mutants of adenovirus type 5. Cell 13, 181–188.[CrossRef]
    [Google Scholar]
  19. Jones, N. C. & Shenk, T. ( 1979; ). Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell 17, 683–689.[CrossRef]
    [Google Scholar]
  20. Kanopka, A., Muhlemann, O. & Akusjärvi, G. ( 1996; ). Inhibition by SR proteins of splicing of a regulated adenovirus pre-mRNA. Nature 381, 535–538.[CrossRef]
    [Google Scholar]
  21. Kao, C. C., Yew, P. R. & Berk, A. J. ( 1990; ). Domains required for in vitro association between the cellular p53 and the adenovirus 2 E1B 55K proteins. Virology 179, 806–814.[CrossRef]
    [Google Scholar]
  22. König, C., Roth, J. & Dobbelstein, M. ( 1999; ). Adenovirus type 5 E4orf3 protein relieves p53 inhibition by E1B-55-kilodalton protein. J Virol 73, 2253–2262.
    [Google Scholar]
  23. Lavau, C., Marchio, A., Fagioli, M. & 7 other authors ( 1995; ). The acute promyelocytic leukaemia-associated PML gene is induced by interferon. Oncogene 11, 871–876.
    [Google Scholar]
  24. Leppard, K. N. ( 1998; ). Regulated RNA processing and RNA transport during adenovirus infection. Semin Virol 8, 301–307.[CrossRef]
    [Google Scholar]
  25. Leppard, K. N. & Shenk, T. ( 1989; ). The adenovirus E1b 55 kd protein influences mRNA transport via an intranuclear effect on RNA metabolism. EMBO J 8, 2329–2336.
    [Google Scholar]
  26. Leppard, K. N. & Everett, R. D. ( 1999; ). The adenovirus type 5 E1b 55K and E4 Orf3 proteins associate in infected cells and affect ND10 components. J Gen Virol 80, 997–1008.
    [Google Scholar]
  27. Müller, S., Matunis, M. J. & Dejean, A. ( 1998; ). Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J 17, 61–70.[CrossRef]
    [Google Scholar]
  28. Negorev, D. & Maul, G. G. ( 2001; ). Cellular proteins localized at and interacting within ND10/PML nuclear bodies/PODs suggest functions of a nuclear depot. Oncogene 20, 7234–7242.[CrossRef]
    [Google Scholar]
  29. Nevels, M., Tauber, B., Kremmer, E., Spruss, T., Wolf, H. & Dobner, T. ( 1999; ). Transforming potential of the adenovirus type 5 E4orf3 protein. J Virol 73, 1591–1600.
    [Google Scholar]
  30. Obert, S., O'Connor, R. J., Schmid, S. & Hearing, P. ( 1994; ). The adenovirus E4–6/7 protein transactivates the E2 promoter by inducing dimerization of a heteromeric E2F complex. Mol Cell Biol 14, 1333–1346.
    [Google Scholar]
  31. Ornelles, D. A. & Shenk, T. ( 1991; ). Localization of the adenovirus early region 1B 55-kilodalton protein during lytic infection: association with nuclear viral inclusions requires the early region 4 34-kilodalton protein. J Virol 65, 424–439.
    [Google Scholar]
  32. Pilder, S., Moore, M., Logan, J. & Shenk, T. ( 1986; ). The adenovirus E1B-55K transforming polypeptide modulates transport or cytoplasmic stabilization of viral and host cell mRNAs. Mol Cell Biol 6, 470–476.
    [Google Scholar]
  33. Regad, T. & Chelbi-Alix, M. K. ( 2001; ). Role and fate of PML nuclear bodies in response to interferon and viral infections. Oncogene 20, 7274–7286.[CrossRef]
    [Google Scholar]
  34. Rubenwolf, S., Schütt, H., Nevels, M., Wolf, H. & Dobner, T. ( 1997; ). Structural analysis of the adenovirus type 5 E1B 55-kilodalton–E4orf6 protein complex. J Virol 71, 1115–1123.
    [Google Scholar]
  35. Sarnow, P., Ho, Y. S., Williams, J. & Levine, A. J. ( 1982a; ). Adenovirus E1b-58kd tumor antigen and SV40 large tumor antigen are physically associated with the same 54 kd cellular protein in transformed cells. Cell 28, 387–394.[CrossRef]
    [Google Scholar]
  36. Sarnow, P., Sullivan, C. A. & Levine, A. J. ( 1982b; ). A monoclonal antibody detecting the adenovirus type 5-E1b-58Kd tumor antigen: characterization of the E1b 58K tumor antigen in adenovirus-infected and -transformed cells. Virology 120, 510–517.[CrossRef]
    [Google Scholar]
  37. Sarnow, P., Hearing, P., Anderson, C. W., Halbert, D. N., Shenk, T. & Levine, A. J. ( 1984; ). Adenovirus early region 1B 58,000-dalton tumor antigen is physically associated with an early region 4 25,000-dalton protein in productively infected cells. J Virol 49, 692–700.
    [Google Scholar]
  38. Seeler, J. S. & Dejean, A. ( 2001; ). SUMO: of branched proteins and nuclear bodies. Oncogene 20, 7243–7249.[CrossRef]
    [Google Scholar]
  39. Shtrichman, R. & Kleinberger, T. ( 1998; ). Adenovirus type 5 E4 open reading frame 4 protein induces apoptosis in transformed cells. J Virol 72, 2975–2982.
    [Google Scholar]
  40. Sternsdorf, T., Jensen, K. & Will, H. ( 1997; ). Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. J Cell Biol 139, 1621–1634.[CrossRef]
    [Google Scholar]
  41. Stracker, T. H., Carson, C. T. & Weitzman, M. D. ( 2002; ). Adenovirus oncoproteins inactivate the Mre11–Rad50–NBS1 DNA repair complex. Nature 418, 348–352.[CrossRef]
    [Google Scholar]
  42. Thimmappaya, B., Weinberger, C., Schneider, R. J. & Shenk, T. ( 1982; ). Adenovirus VAI RNA is required for efficient translation of viral mRNAs at late times after infection. Cell 31, 543–551.[CrossRef]
    [Google Scholar]
  43. Yew, P. R. & Berk, A. J. ( 1992; ). Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature 357, 82–85.[CrossRef]
    [Google Scholar]
  44. Yew, P. R., Kao, C. C. & Berk, A. J. ( 1990; ). Dissection of functional domains in the adenovirus 2 early 1B 55K polypeptide by suppressor-linker insertional mutagenesis. Virology 179, 795–805.[CrossRef]
    [Google Scholar]
  45. Zantema, A., Fransen, J. A. M., Davis-Olivier, A., Ramaekers, F. C. S., Vooijs, G. P., DeLeys, B. & Van der Eb, A. J. ( 1985; ). Localization of the E1B proteins of adenovirus 5 in transformed cells, as revealed by interaction with monoclonal antibodies. Virology 142, 44–58.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.18820-0
Loading
/content/journal/jgv/10.1099/vir.0.18820-0
Loading

Data & Media loading...

Most Cited This Month

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