1887

Abstract

Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. The virus is highly prevalent: 60–80 % of adults are seropositive; however, cells permissive for MCPyV infection are unknown. Consequently, very little information about the MCPyV life cycle is available. Until recently, MCPyV replication could only be studied using a semi-permissive in vitro replication system (Neumann et al., 2011; Feng et al., 2011, Schowalter et al., 2011). MCPyV replication most likely depends on subnuclear structures such as promyelocytic leukemia protein nuclear bodies (PML-NBs), which are known to play regulatory roles in the infection of many DNA viruses. Here, we investigated PML-NB components as candidate host factors to control MCPyV DNA replication. We showed that PML-NBs change in number and size in cells actively replicating MCPyV proviral DNA. We observed a significant increase in PML-NBs in cells positive for MCPyV viral DNA replication. Interestingly, a significant amount of cells actively replicating MCPyV did not show any Sp100 expression. While PML and Daxx had no effect on MCPyV DNA replication, MCPyV replication was increased in cells depleted for Sp100, strongly suggesting that Sp100 is a negative regulator of MCPyV DNA replication.

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2016-11-10
2019-10-14
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References

  1. Adamson A. L., Kenney S..( 2001;). Epstein-barr virus immediate-early protein BZLF1 is SUMO-1 modified and disrupts promyelocytic leukemia bodies. . J Virol 75: 2388–2399. [CrossRef] [PubMed]
    [Google Scholar]
  2. Batty E., Jensen K., Freemont P..( 2009;). PML nuclear bodies and their spatial relationships in the mammalian cell nucleus. . Front Biosci 14: 1182–1196. [CrossRef]
    [Google Scholar]
  3. Bernardi R., Papa A., Pandolfi P. P..( 2008;). Regulation of apoptosis by PML and the PML-NBs. . Oncogene 27: 6299–6312. [CrossRef] [PubMed]
    [Google Scholar]
  4. Berscheminski J., Groitl P., Dobner T., Wimmer P., Schreiner S..( 2013;). The adenoviral oncogene E1A-13S interacts with a specific isoform of the tumor suppressor PML to enhance viral transcription. . J Virol 87: 965–977. [CrossRef] [PubMed]
    [Google Scholar]
  5. Boichuk S., Hu L., Makielski K., Pandolfi P. P., Gjoerup O. V..( 2011;). Functional connection between Rad51 and PML in homology-directed repair. . PLoS One 6: e25814. [CrossRef] [PubMed]
    [Google Scholar]
  6. Borchert S., Czech-Sioli M., Neumann F., Schmidt C., Wimmer P., Dobner T., Grundhoff A., Fischer N..( 2014;). High-affinity Rb binding, p53 inhibition, subcellular localization, and transformation by wild-type or tumor-derived shortened Merkel cell polyomavirus large T antigens. . J Virol 88: 3144–3160. [CrossRef] [PubMed]
    [Google Scholar]
  7. Chang Y., Moore P. S..( 2012;). Merkel cell carcinoma: a virus-induced human cancer. . Annu Rev Pathol 7: 123–144. [CrossRef] [PubMed]
    [Google Scholar]
  8. Chelbi-Alix M. K., Quignon F., Pelicano L., Koken M. H., de Thé H..( 1998;). Resistance to virus infection conferred by the interferon-induced promyelocytic leukemia protein. . J Virol 72: 1043–1051.[PubMed]
    [Google Scholar]
  9. Dellaire G., Bazett-Jones D. P..( 2004;). PML nuclear bodies: dynamic sensors of DNA damage and cellular stress. . Bioessays 26: 963–977. [CrossRef] [PubMed]
    [Google Scholar]
  10. Erickson K. D., Bouchet-Marquis C., Heiser K., Szomolanyi-Tsuda E., Mishra R., Lamothe B., Hoenger A., Garcea R. L..( 2012;). Virion assembly factories in the nucleus of polyomavirus-infected cells. . PLoS Pathog 8: e1002630. [CrossRef] [PubMed]
    [Google Scholar]
  11. Eskiw C. H., Dellaire G., Mymryk J. S., Bazett-Jones D. P..( 2003;). Size, position and dynamic behavior of PML nuclear bodies following cell stress as a paradigm for supramolecular trafficking and assembly. . J Cell Sci 116: 4455–4466. [CrossRef] [PubMed]
    [Google Scholar]
  12. Eskiw C. H., Dellaire G., Bazett-Jones D. P..( 2004;). Chromatin contributes to structural integrity of promyelocytic leukemia bodies through a SUMO-1-independent mechanism. . J Biol Chem 279: 9577–9585. [CrossRef] [PubMed]
    [Google Scholar]
  13. Everett R. D., Lomonte P., Sternsdorf T., van Driel R., Orr A..( 1999;). Cell cycle regulation of PML modification and ND10 composition. . J Cell Sci 24: 4581–4588.
    [Google Scholar]
  14. Everett R. D..( 2001;). DNA viruses and viral proteins that interact with PML nuclear bodies. . Oncogene 20: 7266–7273. [CrossRef] [PubMed]
    [Google Scholar]
  15. Everett R. D., Chelbi-Alix M. K..( 2007;). PML and PML nuclear bodies: implications in antiviral defence. . Biochimie 89: 819–830. [CrossRef] [PubMed]
    [Google Scholar]
  16. Everett R. D., Parada C., Gripon P., Sirma H., Orr A..( 2008;). Replication of ICP0-null mutant herpes simplex virus type 1 is restricted by both PML and Sp100. . J Virol 82: 2661–2672. [CrossRef] [PubMed]
    [Google Scholar]
  17. Feng H., Shuda M., Chang Y., Moore P. S..( 2008;). Clonal integration of a polyomavirus in human Merkel cell carcinoma. . Science 319: 1096–1100. [CrossRef] [PubMed]
    [Google Scholar]
  18. Feng H., Kwun H. J., Liu X., Gjoerup O., Stolz D. B., Chang Y., Moore P. S..( 2011;). Cellular and viral factors regulating Merkel cell polyomavirus replication. . PLoS One 6: e22468. [CrossRef] [PubMed]
    [Google Scholar]
  19. Full F., Reuter N., Zielke K., Stamminger T., Ensser A..( 2012;). Herpesvirus saimiri antagonizes nuclear domain 10-instituted intrinsic immunity via an ORF3-mediated selective degradation of cellular protein Sp100. . J Virol 86: 3541–3553. [CrossRef] [PubMed]
    [Google Scholar]
  20. Gasparovic M. L., Maginnis M. S., O'Hara B. A., Dugan A. S., Atwood W. J..( 2009;). Modulation of PML protein expression regulates JCV infection. . Virology 390: 279–288. [CrossRef] [PubMed]
    [Google Scholar]
  21. Geoffroy M. C., Chelbi-Alix M. K..( 2011;). Role of promyelocytic leukemia protein in host antiviral defense. . J Interferon Cytokine Res 31: 145–158. [CrossRef] [PubMed]
    [Google Scholar]
  22. Grundhoff A., Fischer N..( 2015;). Merkel cell polyomavirus, a highly prevalent virus with tumorigenic potential. . Curr Opin Virol 14: 129–137. [CrossRef] [PubMed]
    [Google Scholar]
  23. Hwang J., Kalejta R. F..( 2007;). Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells. . Virology 367: 334–338. [CrossRef] [PubMed]
    [Google Scholar]
  24. Ishov A. M., Maul G. G..( 1996;). The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. . J Cell Biol 134: 815–826. [CrossRef] [PubMed]
    [Google Scholar]
  25. Jiang M., Abend J. R., Tsai B., Imperiale M. J..( 2009;). Early events during BK virus entry and disassembly. . J Virol 83: 1350–1358. [CrossRef] [PubMed]
    [Google Scholar]
  26. Jiang M., Entezami P., Gamez M., Stamminger T., Imperiale M. J..( 2011;). Functional reorganization of promyelocytic leukemia nuclear bodies during BK virus infection. . MBio 2: e0028100210. [CrossRef] [PubMed]
    [Google Scholar]
  27. Li J., Diaz J., Wang X., Tsang S. H., You J..( 2015;). Phosphorylation of merkel cell polyomavirus large tumor antigen at serine 816 by ATM kinase induces apoptosis in host cells. . J Biol Chem 290: 1874–1884. [CrossRef] [PubMed]
    [Google Scholar]
  28. Liu W., Yang R., Payne A. S., Schowalter R. M., Spurgeon M. E., Lambert P. F., Xu X., Buck C. B., You J..( 2016;). Identifying the target cells and mechanisms of merkel cell polyomavirus infection. . Cell Host Microbe 19: 775–787. [CrossRef] [PubMed]
    [Google Scholar]
  29. Liu X., Hein J., Richardson S. C., Basse P. H., Toptan T., Moore P. S., Gjoerup O. V., Chang Y..( 2011;). Merkel cell polyomavirus large T antigen disrupts lysosome clustering by translocating human Vam6p from the cytoplasm to the nucleus. . J Biol Chem 286: 17079–17090. [CrossRef] [PubMed]
    [Google Scholar]
  30. Lukashchuk V., Everett R. D..( 2010;). Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10 components ATRX and hDaxx. . J Virol 84: 4026–4040. [CrossRef] [PubMed]
    [Google Scholar]
  31. McBride A. A., Jang M. K..( 2013;). Current understanding of the role of the Brd4 protein in the papillomavirus lifecycle. . Viruses 5: 1374–1394. [CrossRef] [PubMed]
    [Google Scholar]
  32. Mitsudomi T., Steinberg S. M., Nau M. M., Carbone D., D'Amico D., Bodner S., Oie H. K., Linnoila R. I., Mulshine J. L. et al.( 1992;). p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. . Oncogene 7: 171–180.[PubMed]
    [Google Scholar]
  33. Neu U., Hengel H., Blaum B. S., Schowalter R. M., Macejak D., Gilbert M., Wakarchuk W. W., Imamura A., Ando H. et al.( 2012;). Structures of Merkel cell polyomavirus VP1 complexes define a sialic acid binding site required for infection. . PLoS Pathog 8: e1002738. [CrossRef] [PubMed]
    [Google Scholar]
  34. Neumann F., Borchert S., Schmidt C., Reimer R., Hohenberg H., Fischer N., Grundhoff A..( 2011;). Replication, gene expression and particle production by a consensus Merkel cell polyomavirus (MCPyV) genome. . PLoS One 6: e29112. [CrossRef] [PubMed]
    [Google Scholar]
  35. Neumann F., Czech-Sioli M., Grundhoff A., Fischer N..( 2015;). In vitro replication assay for Merkel cell polyomavirus (MCPyV). . Curr Protoc Microbiol 38: 14F .2. 1–14F .2. 19.[CrossRef]
    [Google Scholar]
  36. Pastrana D. V., Tolstov Y. L., Becker J. C., Moore P. S., Chang Y., Buck C. B..( 2009;). Quantitation of human seroresponsiveness to Merkel cell polyomavirus. . PLoS Pathog 5: e1000578. [CrossRef] [PubMed]
    [Google Scholar]
  37. Radhakrishnan S., Otte J., Enam S., Del Valle L., Khalili K., Gordon J..( 2003;). JC virus-induced changes in cellular gene expression in primary human astrocytes. . J Virol 77: 10638–10644. [CrossRef] [PubMed]
    [Google Scholar]
  38. Regad T., Saib A., Lallemand-Breitenbach V., Pandolfi P. P., de Thé H., Chelbi-Alix M. K..( 2001;). PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator. . EMBO J 20: 3495–3505. [CrossRef] [PubMed]
    [Google Scholar]
  39. Rozenblatt-Rosen O., Deo R. C., Padi M., Adelmant G., Calderwood M. A., Rolland T., Grace M., Dricot A., Askenazi M. et al.( 2012;). Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. . Nature 487: 491–495. [CrossRef] [PubMed]
    [Google Scholar]
  40. Schowalter R. M., Pastrana D. V., Buck C. B..( 2011;). Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry. . PLoS Pathog 7: e1002161. [CrossRef] [PubMed]
    [Google Scholar]
  41. Schreiner S., Wimmer P., Sirma H., Everett R. D., Blanchette P., Groitl P., Dobner T..( 2010;). Proteasome-dependent degradation of Daxx by the viral E1B-55K protein in human adenovirus-infected cells. . J Virol 84: 7029–7038. [CrossRef] [PubMed]
    [Google Scholar]
  42. Schreiner S., Wimmer P., Groitl P., Chen S. Y., Blanchette P., Branton P. E., Dobner T..( 2011;). Adenovirus type 5 early region 1B 55K oncoprotein-dependent degradation of cellular factor Daxx is required for efficient transformation of primary rodent cells. . J Virol 85: 8752–8765. [CrossRef] [PubMed]
    [Google Scholar]
  43. Schreiner S., Wimmer P., Dobner T..( 2012;). Adenovirus degradation of cellular proteins. . Future Microbiol 7: 211–225. [CrossRef] [PubMed]
    [Google Scholar]
  44. Shuda M., Arora R., Kwun H. J., Feng H., Sarid R., Fernández-Figueras M. T., Tolstov Y., Gjoerup O., Mansukhani M. M. et al.( 2009;). Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. . Int J Cancer 125: 1243–1249. [CrossRef] [PubMed]
    [Google Scholar]
  45. Tang Q., Bell P., Tegtmeyer P., Maul G. G..( 2000;). Replication but not transcription of simian virus 40 DNA is dependent on nuclear domain 10. . J Virol 74: 9694–9700. [CrossRef] [PubMed]
    [Google Scholar]
  46. Tavalai N., Stamminger T..( 2008;). New insights into the role of the subnuclear structure ND10 for viral infection. . Biochim Biophys Acta 1783: 2207–2221. [CrossRef] [PubMed]
    [Google Scholar]
  47. Torok D., Ching R. W., Bazett-Jones D. P..( 2009;). PML nuclear bodies as sites of epigenetic regulation. . Front Biosci 14: 1325–1336. [CrossRef]
    [Google Scholar]
  48. Van Damme E., Laukens K., Dang T. H., Van Ostade X..( 2010;). A manually curated network of the PML nuclear body interactome reveals an important role for PML-NBs in SUMOylation dynamics. . Int J Biol Sci 6: 51–67. [CrossRef] [PubMed]
    [Google Scholar]
  49. Wang S., Long J., Zheng C. F..( 2012a;). The potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1. . Protein Cell 3: 372–382. [CrossRef]
    [Google Scholar]
  50. Wang X., Li J., Schowalter R. M., Jiao J., Buck C. B., You J..( 2012b;). Bromodomain protein brd4 plays a key role in merkel cell polyomavirus DNA replication. . PLoS Pathogens 8: e1003021. [CrossRef]
    [Google Scholar]
  51. Weidner-Glunde M., Ottinger M., Schulz T. F..( 2010;). WHAT do viruses BET on?. Front Biosci 15: 537–549. [CrossRef]
    [Google Scholar]
  52. Wendzicki J. A., Moore P. S., Chang Y..( 2015;). Large T and small T antigens of Merkel cell polyomavirus. . Curr Opin Virol 11: 38–43. [CrossRef] [PubMed]
    [Google Scholar]
  53. White M. K., Khalili K..( 2004;). Polyomaviruses and human cancer: molecular mechanisms underlying patterns of tumorigenesis. . Virology 324: 1–16. [CrossRef] [PubMed]
    [Google Scholar]
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