1887

Abstract

Human cytomegalovirus (HCMV) is a frequent cause of major disease following primary infection or reactivation from latency in immunocompromised patients. Infection of non-permissive mononuclear cells is used for analyses of HCMV latency . Using this approach, it is shown here that repression of lytic gene expression following experimental infection of CD34 cells, a site of HCMV latency , correlates with recruitment of repressive chromatin around the major immediate-early promoter (MIEP). Furthermore, long-term culture of CD34 cells results in carriage of viral genomes in which the MIEP remains associated with transcriptionally repressive chromatin. Finally, specific differentiation of long-term cultures of infected CD34 cells to mature dendritic cells results in acetylation of histones bound to the MIEP, concomitant loss of heterochromatin protein 1 and the reactivation of HCMV. These data are consistent with analyses of latency and may provide a model for further analyses of the mechanisms involved during latency and reactivation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81161-0
2005-11-01
2020-09-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/11/2949.html?itemId=/content/journal/jgv/10.1099/vir.0.81161-0&mimeType=html&fmt=ahah

References

  1. Adler S. P. 1983; Transfusion-associated cytomegalovirus infections. Rev Infect Dis 5:977–993 [CrossRef]
    [Google Scholar]
  2. Bain M., Mendelson M., Sinclair J. 2003; Ets-2 Repressor Factor (ERF) mediates repression of the human cytomegalovirus major immediate-early promoter in undifferentiated non-permissive cells. J Gen Virol 84:41–49 [CrossRef]
    [Google Scholar]
  3. Bannister A. J., Zegerman P., Partridge J. F., Miska E. A., Thomas J. O., Allshire R. C., Kouzarides T. 2001; Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124 [CrossRef]
    [Google Scholar]
  4. Bevan I. S., Daw R. A., Day P. J., Ala F. A., Walker M. R. 1991; Polymerase chain reaction for detection of human cytomegalovirus infection in a blood donor population. Br J Haematol 78:94–99 [CrossRef]
    [Google Scholar]
  5. Davison A. J., Dolan A., Atker P., Addison C., Dargan D. J., Alcendor D. J., McGeoch D. J., Hayward G. S. 2003; The human cytomegalovirus genome revisited: comparison with the chimpanzee cytomegalovirus genome. J Gen Virol 84:17–28 [CrossRef]
    [Google Scholar]
  6. DeMeritt I. B., Milford L. E., Yurochko A. D. 2004; Activation of the NF- κ B pathway in human cytomegalovirus-infected cells is necessary for efficient transactivation of the major immediate-early promoter. J Virol 78:4498–4507 [CrossRef]
    [Google Scholar]
  7. Goodrum F., Jordan C. T., Terhune S. S., High K., Shenk T. 2004; Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations. Blood104687–695 [CrossRef]
  8. Hahn G., Jores R., Mocarski E. S. 1998; Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci U S A 95:3937–3942 [CrossRef]
    [Google Scholar]
  9. Hertel L., Lacaille V. G., Strobl H., Mellins E. D., Mocarski E. S. 2003; Susceptibility of immature and mature Langerhans cell-type dendritic cells to infection and immunomodulation by human cytomegalovirus. J Virol 77:7563–7574 [CrossRef]
    [Google Scholar]
  10. Hummel M., Abecassis M. M. 2002; A model for reactivation of CMV from latency. J Clin Virol 25 (Suppl. 2):S123–S136 [CrossRef]
    [Google Scholar]
  11. Jenkins C., Abendroth A., Slobedman B. 2004; A novel viral transcript with homology to human interleukin-10 is expressed during latent human cytomegalovirus infection. J Virol 78:1440–1447 [CrossRef]
    [Google Scholar]
  12. Kondo K., Kaneshima H., Mocarski E. S. 1994; Human cytomegalovirus latent infection of granulocyte–macrophage progenitors. Proc Natl Acad Sci U S A 91:11879–11883 [CrossRef]
    [Google Scholar]
  13. Kondo K., Xu J., Mocarski E. S. 1996; Human cytomegalovirus latent gene expression in granulocyte–macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci U S A 93:11137–11142 [CrossRef]
    [Google Scholar]
  14. Liu R., Baillie J., Sissons J. G. P., Sinclair J. H. 1994; The transcription factor YY1 binds to negative regulatory elements in the human cytomegalovirus major immediate early enhancer/promoter and mediates repression in non-permissive cells. Nucleic Acids Res 22:2453–2459 [CrossRef]
    [Google Scholar]
  15. Luo R. X., Postigo A. A., Dean D. C. 1998; Rb interacts with histone deacetylase to repress transcription. Cell 92:463–473 [CrossRef]
    [Google Scholar]
  16. Lusser A. 2002; Acetylated, methylated, remodeled: chromatin states for gene regulation. Curr Opin Plant Biol 5:437–443 [CrossRef]
    [Google Scholar]
  17. Lutterbach B., Hiebert S. W. 2000; Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene 245:223–235 [CrossRef]
    [Google Scholar]
  18. MacAry P. A., Lindsay M., Scott M. A., Craig J. I. O., Luzio J. P., Lehner P. J. 2001; Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells. Proc Natl Acad Sci U S A 98:3982–3987 [CrossRef]
    [Google Scholar]
  19. Maciejewski J. P., St Jeor S. C. 1999; Human cytomegalovirus infection of human hematopoietic progenitor cells. Leuk Lymphoma 33:1–13
    [Google Scholar]
  20. Mendelson M., Monard S., Sissons P., Sinclair J. 1996; Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol 77:3099–3102 [CrossRef]
    [Google Scholar]
  21. Minton E. J., Tysoe C., Sinclair J. H., Sissons J. G. P. 1994; Human cytomegalovirus infection of the monocyte/macrophage lineage in bone marrow. J Virol 68:4017–4021
    [Google Scholar]
  22. Movassagh M., Gozlan J., Senechal B., Baillou C., Petit J.-C., Lemoine F. M. 1996; Direct infection of CD34+ progenitor cells by human cytomegalovirus: evidence for inhibition of hematopoiesis and viral replication. Blood 88:1277–1283
    [Google Scholar]
  23. Murphy J. C., Fischle W., Verdin E., Sinclair J. H. 2002; Control of cytomegalovirus lytic gene expression by histone acetylation. EMBO J 21:1112–1120 [CrossRef]
    [Google Scholar]
  24. Reeves M. B., MacAry P. A., Lehner P. J., Sissons J. G. P., Sinclair J. H. 2005; Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc Natl Acad Sci U S A 102:4140–4145 [CrossRef]
    [Google Scholar]
  25. Rezai-Zadeh N., Zhang X., Namour F., Fejer G., Wen Y.-D., Yao Y.-L., Gyory I., Wright K., Seto E. 2003; Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1. Genes Dev 17:1019–1029 [CrossRef]
    [Google Scholar]
  26. Rubin R. H. 1990; Impact of cytomegalovirus infection on organ transplant recipients. Rev Infect Dis 12 (Suppl. 7):S754–S766 [CrossRef]
    [Google Scholar]
  27. Saccani S., Pantano S., Natoli G. 2002; p38-dependent marking of inflammatory genes for increased NF- κ B recruitment. Nat Immunol 3:69–75 [CrossRef]
    [Google Scholar]
  28. Simon C. O., Seckert C. K., Dreis D., Reddehase M. J., Grzimek N. K. A. 2005; Role for tumor necrosis factor alpha in murine cytomegalovirus transcriptional reactivation in latently infected lungs. J Virol 79:326–340 [CrossRef]
    [Google Scholar]
  29. Sinclair J., Sissons P. 1996; Latent and persistent infections of monocytes and macrophages. Intervirology 39:293–301
    [Google Scholar]
  30. Sindre H., Tjønnfjord G. E., Rollag H., Ranneberg-Nilsen T., Veiby O. P., Beck S., Degré M., Hestdal K. 1996; Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells. Blood 88:4526–4533
    [Google Scholar]
  31. Slobedman B., Mocarski E. S. 1999; Quantitative analysis of latent human cytomegalovirus. J Virol 73:4806–4812
    [Google Scholar]
  32. Slobedman B., Stern J. L., Cunningham A. L., Abendroth A., Abate D. A., Mocarski E. S. 2004; Impact of human cytomegalovirus latent infection on myeloid progenitor cell gene expression. J Virol 78:4054–4062 [CrossRef]
    [Google Scholar]
  33. Söderberg-Nauclér C., Nelson J. A. 1999; Human cytomegalovirus latency and reactivation – a delicate balance between the virus and its host's immune system. Intervirology 42:314–321 [CrossRef]
    [Google Scholar]
  34. Söderberg-Nauclér C., Fish K. N., Nelson J. A. 1997; Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell 91:119–126 [CrossRef]
    [Google Scholar]
  35. Strahl B. D., Allis C. D. 2000; The language of covalent histone modifications. Nature 403:41–45 [CrossRef]
    [Google Scholar]
  36. Strobl H., Bello-Fernandez C., Riedl E., Pickl W. F., Majdic O., Lyman S. D., Knapp W. 1997; flt3 ligand in cooperation with transforming growth factor- β 1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90:1425–1434
    [Google Scholar]
  37. Taniguchi Y., Kitagawa Y. 1996; Repressor-like factor that interacts with SV40 promoter/enhancer and expressed during differentiation of embryonal carcinoma F9 cells. Biosci Biotechnol Biochem 60:721–723 [CrossRef]
    [Google Scholar]
  38. Taylor-Wiedeman J., Sissons J. G. P., Borysiewicz L. K., Sinclair J. H. 1991; Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol 72:2059–2064 [CrossRef]
    [Google Scholar]
  39. Taylor-Wiedeman J., Sissons P., Sinclair J. 1994; Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol 68:1597–1604
    [Google Scholar]
  40. Wright E., Bain M., Teague L., Murphy J., Sinclair J. 2005; Ets-2 repressor factor recruits histone deacetylase to silence human cytomegalovirus immediate-early gene expression in non-permissive cells. J Gen Virol 86:535–544 [CrossRef]
    [Google Scholar]
  41. Yang W.-M., Inouye C., Zeng Y., Bearss D., Seto E. 1996; Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Proc Natl Acad Sci U S A 93:12845–12850 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81161-0
Loading
/content/journal/jgv/10.1099/vir.0.81161-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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