1887

Abstract

Nuclear domains 10 (ND10s) are discrete subnuclear structures that contain the three major protein components promyelocytic leukaemia protein (PML), hDaxx and Sp100. Previous studies identified the ND10-components PML and hDaxx as cellular restriction factors that independently counteract human cytomegalovirus (HCMV) infection via the repression of viral immediate-early (IE) gene expression. Consequently, we asked whether Sp100 is likewise involved in this repressive activity. Infection of Sp100 knockdown (kd) cells with HCMV resulted in a significantly increased plaque-forming ability. In addition, ablation of Sp100 led to a considerable increase in the number of IE1-expressing cells, indicating that Sp100 suppresses the initiation of viral gene expression. Next, double-kd cells, lacking either Sp100/hDaxx or Sp100/PML, were generated. Here, infection resulted in an additional enhancement in HCMV replication efficacy compared with the single-kd cells. Thus, our results further strengthen the concept that the three major ND10-components independently contribute to the cellular restriction of HCMV replication.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.030981-0
2011-07-01
2019-10-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/7/1532.html?itemId=/content/journal/jgv/10.1099/vir.0.030981-0&mimeType=html&fmt=ahah

References

  1. Andreoni M. , Faircloth M. , Vugler L. , Britt W. J. . ( 1989; ). A rapid microneutralization assay for the measurement of neutralizing antibody reactive with human cytomegalovirus. . J Virol Methods 23:, 157–167. [CrossRef].[PubMed]
    [Google Scholar]
  2. Bieniasz P. D. . ( 2004; ). Intrinsic immunity: a front-line defense against viral attack. . Nat Immunol 5:, 1109–1115. [CrossRef].[PubMed]
    [Google Scholar]
  3. Cantrell S. R. , Bresnahan W. A. . ( 2006; ). Human cytomegalovirus (HCMV) UL82 gene product (pp71) relieves hDaxx-mediated repression of HCMV replication. . J Virol 80:, 6188–6191. [CrossRef].[PubMed]
    [Google Scholar]
  4. Cuchet D. , Sykes A. , Nicolas A. , Orr A. , Murray J. , Sirma H. , Heeren J. , Bartelt A. , Everett R. D. . ( 2011; ). PML isoforms I and II participate in PML-dependent restriction of HSV-1 replication. . J Cell Sci 124:, 280–291. [CrossRef].[PubMed]
    [Google Scholar]
  5. de la Hoz R. E. , Stephens G. , Sherlock C. . ( 2002; ). Diagnosis and treatment approaches of CMV infections in adult patients. . J Clin Virol 25: (Suppl. 2), S1–S12. [CrossRef].[PubMed]
    [Google Scholar]
  6. Dent A. L. , Yewdell J. , Puvion-Dutilleul F. , Koken M. H. , de The H. , Staudt L. M. . ( 1996; ). LYSP100-associated nuclear domains (LANDs): description of a new class of subnuclear structures and their relationship to PML nuclear bodies. . Blood 88:, 1423–1426.[PubMed]
    [Google Scholar]
  7. 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]
  8. Everett R. D. , Rechter S. , Papior P. , Tavalai N. , Stamminger T. , Orr A. . ( 2006; ). PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0. . J Virol 80:, 7995–8005. [CrossRef].[PubMed]
    [Google Scholar]
  9. 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]
  10. Guldner H. H. , Szostecki C. , Grötzinger T. , Will H. . ( 1992; ). IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. . J Immunol 149:, 4067–4073.[PubMed]
    [Google Scholar]
  11. Guldner H. H. , Szostecki C. , Schröder P. , Matschl U. , Jensen K. , Lüders C. , Will H. , Sternsdorf T. . ( 1999; ). Splice variants of the nuclear dot-associated Sp100 protein contain homologies to HMG-1 and a human nuclear phosphoprotein-box motif. . J Cell Sci 112:, 733–747.[PubMed]
    [Google Scholar]
  12. Ishov A. M. , Sotnikov A. G. , Negorev D. , Vladimirova O. V. , Neff N. , Kamitani T. , Yeh E. T. , Strauss J. F. III , Maul G. G. . ( 1999; ). PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. . J Cell Biol 147:, 221–234. [CrossRef].[PubMed]
    [Google Scholar]
  13. Lavau C. , Marchio A. , Fagioli M. , Jansen J. , Falini B. , Lebon P. , Grosveld F. , Pandolfi P. P. , Pelicci P. G. , Dejean A. . ( 1995; ). The acute promyelocytic leukaemia-associated PML gene is induced by interferon. . Oncogene 11:, 871–876.[PubMed]
    [Google Scholar]
  14. Marschall M. , Freitag M. , Weiler S. , Sorg G. , Stamminger T. . ( 2000; ). Recombinant green fluorescent protein-expressing human cytomegalovirus as a tool for screening antiviral agents. . Antimicrob Agents Chemother 44:, 1588–1597. [CrossRef].[PubMed]
    [Google Scholar]
  15. Negorev D. G. , Vladimirova O. V. , Maul G. G. . ( 2009; ). Differential functions of interferon-upregulated Sp100 isoforms: herpes simplex virus type 1 promoter-based immediate-early gene suppression and PML protection from ICP0-mediated degradation. . J Virol 83:, 5168–5180. [CrossRef].[PubMed]
    [Google Scholar]
  16. Preston C. M. , Nicholl M. J. . ( 2006; ). Role of the cellular protein hDaxx in human cytomegalovirus immediate-early gene expression. . J Gen Virol 87:, 1113–1121. [CrossRef].[PubMed]
    [Google Scholar]
  17. Saffert R. T. , Kalejta R. F. . ( 2006; ). Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression. . J Virol 80:, 3863–3871. [CrossRef].[PubMed]
    [Google Scholar]
  18. Seeler J. S. , Marchio A. , Losson R. , Desterro J. M. , Hay R. T. , Chambon P. , Dejean A. . ( 2001; ). Common properties of nuclear body protein SP100 and TIF1alpha chromatin factor: role of SUMO modification. . Mol Cell Biol 21:, 3314–3324. [CrossRef].[PubMed]
    [Google Scholar]
  19. Stadler M. , Chelbi-Alix M. K. , Koken M. H. , Venturini L. , Lee C. , Saïb A. , Quignon F. , Pelicano L. , Guillemin M. C. et al. ( 1995; ). Transcriptional induction of the PML growth suppressor gene by interferons is mediated through an ISRE and a GAS element. . Oncogene 11:, 2565–2573.[PubMed]
    [Google Scholar]
  20. Stuurman N. , de Graaf A. , Floore A. , Josso A. , Humbel B. , de Jong L. , van Driel R. . ( 1992; ). A monoclonal antibody recognizing nuclear matrix-associated nuclear bodies. . J Cell Sci 101:, 773–784.[PubMed]
    [Google Scholar]
  21. Szostecki C. , Guldner H. H. , Netter H. J. , Will H. . ( 1990; ). Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. . J Immunol 145:, 4338–4347.[PubMed]
    [Google Scholar]
  22. 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]
  23. Tavalai N. , Stamminger T. . ( 2010; ). Intrinsic cellular defense mechanisms targeting human cytomegalovirus. . Virus Res (In Press). [CrossRef].[PubMed]
    [Google Scholar]
  24. Tavalai N. , Papior P. , Rechter S. , Leis M. , Stamminger T. . ( 2006; ). Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. . J Virol 80:, 8006–8018. [CrossRef].[PubMed]
    [Google Scholar]
  25. Tavalai N. , Papior P. , Rechter S. , Stamminger T. . ( 2008; ). Nuclear domain 10 components promyelocytic leukemia protein and hDaxx independently contribute to an intrinsic antiviral defense against human cytomegalovirus infection. . J Virol 82:, 126–137. [CrossRef].[PubMed]
    [Google Scholar]
  26. 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.[PubMed] [CrossRef]
    [Google Scholar]
  27. Woodhall D. L. , Groves I. J. , Reeves M. B. , Wilkinson G. , Sinclair J. H. . ( 2006; ). Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. . J Biol Chem 281:, 37652–37660. [CrossRef].[PubMed]
    [Google Scholar]
  28. Zhong S. , Müller S. , Ronchetti S. , Freemont P. S. , Dejean A. , Pandolfi P. P. . ( 2000; ). Role of SUMO-1-modified PML in nuclear body formation. . Blood 95:, 2748–2752.[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.030981-0
Loading
/content/journal/jgv/10.1099/vir.0.030981-0
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