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Studies on HOXB4 Expression During Differentiation of Human Cytomegalovirus-infected Hematopoietic Stem Cells into Lymphocyte and Erythrocyte Progenitor Cells

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Abstract

We investigated the role of homeobox B4 (HOXB4) mRNA/protein expression induced by human cytomegalovirus (HCMV) and/or all-trans retinoic acid (ATRA) in proliferation and committed differentiation of human cord blood hematopoietic stem cells (HSCs) into colony-forming-units of T-lymphocyte (CFU-TL) and erythroid (CFU-E) progenitors in vitro. Twelve cord blood samples were collected from the fetal placenta umbilical vein and cultured in vitro. The proliferation and differentiation of cord blood HSCs into CFU-TL and CFU-E were continuously disrupted with HCMV-AD169 and/or 6 × 10−8 mol/l of ATRA. HOXB4 mRNA/protein expression in CFU-TL and CFU-E was detected in control, ATRA, HCMV and ATRA + HCMV groups on days 3, 7, and 12 of culture by fluorescent qRT-PCR/western blot. We found that HOXB4 mRNA/protein expression was detectable on day 3, increased on day 7 and was highest on day 12. HOXB4 mRNA/protein expression in HCMV group was downregulated compared with control group (P < 0.05). However, the levels were significantly upregulated in HCMV + ATRA group compared with HCMV group (P < 0.05). We concluded that the abnormal HOXB4 mRNA/protein expression induced by HCMV could play a role in hematopoietic damage. ATRA, at the concentration used, significantly up-regulated HOXB4 mRNA/protein expression in normal lymphocyte and erythrocyte progenitor cells as well as in HCMV-infected cells.

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References

  1. Zhuravskaya, T., Maciejewski, J. P., Netski, D. M., Bruening, E., Mackintosh, F. R., & St Jeor, S. (1997). Spread of human cytomegalovirus (HCMV) after infection of human hematopoietic progenitor cells: Model of HCMV latency. Blood, 90, 2482–2491.

    PubMed  CAS  Google Scholar 

  2. Cheung, A. K., Abendroth, A., Cunningham, A. L., & Slobedman, B. (2006). Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells. Blood, 108, 3691–3699.

    Article  PubMed  CAS  Google Scholar 

  3. Cheung, A. K., Gottlieb, D. J., Plachter, B., Cunningham, A. L., Abendroth, A., & Slobedman, B. (2009). The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency. Blood, 114, 4128–4137.

    Article  PubMed  CAS  Google Scholar 

  4. Buske, C., Feuring-Buske, M., Abramovich, C., et al. (2002). Deregulated expression of HOXB4 enhances the primitive growth activity of human hematopoietic cells. Blood, 100, 862–868.

    Article  PubMed  CAS  Google Scholar 

  5. Magli, M. C., Barba, P., Celetti, A., De Vita, G., Cillo, C., & E Boncinelli, E. (1991). Coordinate regulation of HOX genes in human hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America, 88, 6348–6352.

    Article  PubMed  CAS  Google Scholar 

  6. Brun, A. C., Bjornsson, J. M., Magnusson, M., et al. (2004). Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. Blood, 103, 4126–4133.

    Article  PubMed  CAS  Google Scholar 

  7. Heise, M. T., White, L. J., Simpson, D. A., et al. (2003). An attenuating mutation in nsP1 of the Sindbis-group virus S.A.AR86 accelerates nonstructural protein processing and up-regulates viral 26S RNA synthesis. Journal of Virology, 77, 1149–1156.

    Article  PubMed  CAS  Google Scholar 

  8. Madi, N., Al-Nakib, W., Mustafa, A. S., Saeed, T., Pacsa, A., & Nampoory, M. R. (2007). Detection and monitoring of cytomegalovirus infection in renal transplant patients by quantitative real-time PCR. Medical Principles and Practice, 16, 268–273.

    Article  PubMed  Google Scholar 

  9. Jurak, I., & Brune, W. (2006). Induction of apoptosis limits cytomegalovirus cross-species infection. EMBO Journal, 25, 2634–2642.

    Article  PubMed  CAS  Google Scholar 

  10. Behzad-Behbahani, A., Entezam, M., Mojiri, A., et al. (2008). Incidence of human herpes virus-6 and human cytomegalovirus infections in donated bone marrow and umbilical cord blood hematopoietic stem cells. Indian Journal of Medical Microbiology, 26, 252–255.

    Article  PubMed  CAS  Google Scholar 

  11. Oshima, M., Endoh, M., Endo, T. A., et al. (2011). Genome-wide analysis of target genes regulated by HoxB4 in hematopoietic stem and progenitor cells developing from embryonic stem cells. Blood, 117, e142–e150.

    Article  PubMed  CAS  Google Scholar 

  12. Bowles, K. M., Vallier, L., Smith, J. R., Alexander, M. R., & Pedersen, R. A. (2006). HOXB4 overexpression promotes hematopoietic development by human embryonic stem cells. Stem Cells, 24, 1359–1369.

    Article  PubMed  CAS  Google Scholar 

  13. Zhu, J., Zhang, Y., Joe, G. J., et al. (2005). NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal. Proceedings of the National Academy of Sciences of the United States of America, 102, 11728–11733.

    Article  PubMed  CAS  Google Scholar 

  14. Beslu, N., Krosl, J., Laurin, M., et al. (2004). Molecular interactions involved in HOXB4-induced activation of HSC self-renewal. Blood, 104, 2307–2314.

    Article  PubMed  CAS  Google Scholar 

  15. Miyake, N., Brun, A. C., Magnusson, M., Miyake, K., Scadden, D. T., & Karlsson, S. (2006). HOXB4-induced self-renewal of hematopoietic stem cells is significantly enhanced by p21 deficiency. Stem Cells, 24, 653–661.

    Article  PubMed  CAS  Google Scholar 

  16. Chen, L. Y., Dai, G., Wu, G. J., et al. (2000). Influence of human cytomegalovirus infection on the expression of HOX genes in human embryo lung cells. Hunan Yi Ke Da Xue Xue Bao, 25, 440–442.

    PubMed  CAS  Google Scholar 

  17. Reeves, M. B. (2011). Chromatin-mediated regulation of cytomegalovirus gene expression. Virus Research, 157, 134–143.

    Article  PubMed  CAS  Google Scholar 

  18. Sinclair, J. (2010). Chromatin structure regulates human cytomegalovirus gene expression during latency, reactivation and lytic infection. Biochimica et Biophysica Acta, 1799, 286–295.

    PubMed  CAS  Google Scholar 

  19. Kirito, K., Fox, N., & Kaushansky, K. (2003). Thrombopoietin stimulates Hoxb4 expression: An explanation for the favorable effects of TPO on hematopoietic stem cells. Blood, 102, 3172–3178.

    Article  PubMed  Google Scholar 

  20. Yurochko, A. D., & Huang, E. S. (1999). Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression. The Journal of Immunology, 162, 4806–4816.

    PubMed  CAS  Google Scholar 

  21. Niu, C. S., Li, M. W., Ni, Y. F., Chen, J. M., Mei, J. M., Li, J., et al. (2010). Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells. Journal of Experimental Clinical Cancer Research, 29, 113.

    Article  PubMed  Google Scholar 

  22. Bel-Vialar, S., Itasaki, N., & Krumlauf, R. (2002). Initiating Hox gene expression in the early chick neural tube differential sensitivity to FGF and RA signaling subdivides the Hoxb genes in two distinct groups. Development, 129, 5103–5115.

    PubMed  CAS  Google Scholar 

  23. Evans, T. (2005). Regulation of hematopoiesis by retinoid signaling. Experimental Hematology, 33, 1055–1061.

    Article  PubMed  CAS  Google Scholar 

  24. Sammons, J., Ahmed, N., Khokher, M. A., & Hassan, H. T. (2000). Mechanisms mediating the inhibitory effect of all-trans retinoic acid on primitive hematopoietic stem cells in human long-term bone marrow culture. Stem Cells, 18, 214–219.

    Article  PubMed  CAS  Google Scholar 

  25. Botto, S., Streblow, D. N., DeFilippis, V., et al. (2011). IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin. Blood, 117, 352–361.

    Article  PubMed  CAS  Google Scholar 

  26. Kirchmeyer, M., Koufany, M., Sebillaud, S., Netter, P., Jouzeau, J. Y., & Bianchi, A. (2008). All-trans retinoic acid suppresses interleukin-6 expression in interleukin-1-stimulated synovial fibroblasts by inhibition of ERK1/2 pathway independently of RAR activation. Arthritis Research and Therapy, 10, R141.

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank the Health Bureau of Sichuan Province for financial support (Grant No. 20060040).

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Correspondence to Liu Wen-jun.

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Wen-jun, L., qu-lian, G., Hong-ying, C. et al. Studies on HOXB4 Expression During Differentiation of Human Cytomegalovirus-infected Hematopoietic Stem Cells into Lymphocyte and Erythrocyte Progenitor Cells. Cell Biochem Biophys 63, 133–141 (2012). https://doi.org/10.1007/s12013-012-9349-y

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