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.

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2005-11-01
2019-12-11
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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-κB 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. Blood 104, 687–695.[CrossRef]
    [Google Scholar]
  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-κB 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-β1 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]
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