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. 1994 Jun;68(6):4017–4021. doi: 10.1128/jvi.68.6.4017-4021.1994

Human cytomegalovirus infection of the monocyte/macrophage lineage in bone marrow.

E J Minton 1, C Tysoe 1, J H Sinclair 1, J G Sissons 1
PMCID: PMC236908  PMID: 8189535

Abstract

Peripheral blood monocytes (PBM) are one site of persistence of human cytomegalovirus (HCMV) in healthy carriers. However, because PBM circulate only briefly before entering the tissues and are difficult to infect with HCMV, it has been suggested that they may acquire HCMV during development in the bone marrow. Consistent with this, we show evidence that bone marrow progenitors from healthy HCMV carriers contain endogenous HCMV DNA as detected by PCR. We also show that bone marrow precursors are readily infected by clinical isolates of HCMV in vitro but that no viral gene expression occurs until these cells become differentiated. In contrast, incubation of these cells at any developmental stage with the laboratory strain AD169 resulted in few cells expressing viral immediate-early genes, and this correlated with a lack of entry of AD169 virus. These observations are consistent with bone marrow progenitors acting as a reservoir for HCMV and transmitting the viral genome to PBM, in the absence of lytic-gene expression, until they leave the circulation and undergo tissue-specific differentiation to macrophages.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apperley J. F., Dowding C., Hibbin J., Buiter J., Matutes E., Sissons P. J., Gordon M., Goldman J. M. The effect of cytomegalovirus on hemopoiesis: in vitro evidence for selective infection of marrow stromal cells. Exp Hematol. 1989 Jan;17(1):38–45. [PubMed] [Google Scholar]
  2. Borysiewicz L. K., Graham S., Hickling J. K., Mason P. D., Sissons J. G. Human cytomegalovirus-specific cytotoxic T cells: their precursor frequency and stage specificity. Eur J Immunol. 1988 Feb;18(2):269–275. doi: 10.1002/eji.1830180214. [DOI] [PubMed] [Google Scholar]
  3. Browne H., Churcher M., Minson T. Construction and characterization of a human cytomegalovirus mutant with the UL18 (class I homolog) gene deleted. J Virol. 1992 Nov;66(11):6784–6787. doi: 10.1128/jvi.66.11.6784-6787.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Corrochano L. M. A test of human cDNA synthesis by the polymerase chain reaction. Genet Anal Tech Appl. 1991 Jun;8(4):134–135. doi: 10.1016/1050-3862(91)90030-u. [DOI] [PubMed] [Google Scholar]
  5. Cranage M. P., Smith G. L., Bell S. E., Hart H., Brown C., Bankier A. T., Tomlinson P., Barrell B. G., Minson T. C. Identification and expression of a human cytomegalovirus glycoprotein with homology to the Epstein-Barr virus BXLF2 product, varicella-zoster virus gpIII, and herpes simplex virus type 1 glycoprotein H. J Virol. 1988 Apr;62(4):1416–1422. doi: 10.1128/jvi.62.4.1416-1422.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drew W. L. Cytomegalovirus infection in patients with AIDS. J Infect Dis. 1988 Aug;158(2):449–456. doi: 10.1093/infdis/158.2.449. [DOI] [PubMed] [Google Scholar]
  7. Drew W. L., Mintz L., Hoo R., Finley T. N. Growth of herpes simplex and cytomegalovirus in cultured human alveolar macrophages. Am Rev Respir Dis. 1979 Feb;119(2):287–291. doi: 10.1164/arrd.1979.119.2.287. [DOI] [PubMed] [Google Scholar]
  8. Einhorn L., Ost A. Cytomegalovirus infection of human blood cells. J Infect Dis. 1984 Feb;149(2):207–214. doi: 10.1093/infdis/149.2.207. [DOI] [PubMed] [Google Scholar]
  9. Gartner S., Kaplan H. S. Long-term culture of human bone marrow cells. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4756–4759. doi: 10.1073/pnas.77.8.4756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gendelman H. E., Narayan O., Kennedy-Stoskopf S., Kennedy P. G., Ghotbi Z., Clements J. E., Stanley J., Pezeshkpour G. Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol. 1986 Apr;58(1):67–74. doi: 10.1128/jvi.58.1.67-74.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ibanez C. E., Schrier R., Ghazal P., Wiley C., Nelson J. A. Human cytomegalovirus productively infects primary differentiated macrophages. J Virol. 1991 Dec;65(12):6581–6588. doi: 10.1128/jvi.65.12.6581-6588.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jordan M. C. Latent infection and the elusive cytomegalovirus. Rev Infect Dis. 1983 Mar-Apr;5(2):205–215. doi: 10.1093/clinids/5.2.205. [DOI] [PubMed] [Google Scholar]
  13. Käriäinen L., Klemola E., Paloheimo J. Rise of cytomegalovirus antibodies in an infectious-mononucleosis-like syndrome after transfusion. Br Med J. 1966 May 21;1(5498):1270–1272. doi: 10.1136/bmj.1.5498.1270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lathey J. L., Spector S. A. Unrestricted replication of human cytomegalovirus in hydrocortisone-treated macrophages. J Virol. 1991 Nov;65(11):6371–6375. doi: 10.1128/jvi.65.11.6371-6375.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Maciejewski J. P., Bruening E. E., Donahue R. E., Mocarski E. S., Young N. S., St Jeor S. C. Infection of hematopoietic progenitor cells by human cytomegalovirus. Blood. 1992 Jul 1;80(1):170–178. [PubMed] [Google Scholar]
  16. Metcalf D. Control of granulocytes and macrophages: molecular, cellular, and clinical aspects. Science. 1991 Oct 25;254(5031):529–533. doi: 10.1126/science.1948028. [DOI] [PubMed] [Google Scholar]
  17. Preiksaitis J. K., Janowska-Wieczorek A. Persistence of cytomegalovirus in human long-term bone marrow culture: relationship to hemopoiesis. J Med Virol. 1991 Oct;35(2):76–84. doi: 10.1002/jmv.1890350203. [DOI] [PubMed] [Google Scholar]
  18. Prince A. M., Szmuness W., Millian S. J., David D. S. A serologic study of cytomegalovirus infections associated with blood transfusions. N Engl J Med. 1971 May 20;284(20):1125–1131. doi: 10.1056/NEJM197105202842004. [DOI] [PubMed] [Google Scholar]
  19. Reiser H., Kühn J., Doerr H. W., Kirchner H., Munk K., Braun R. Human cytomegalovirus replicates in primary human bone marrow cells. J Gen Virol. 1986 Dec;67(Pt 12):2595–2604. doi: 10.1099/0022-1317-67-12-2595. [DOI] [PubMed] [Google Scholar]
  20. Revello M. G., Percivalle E., Di Matteo A., Morini F., Gerna G. Nuclear expression of the lower matrix protein of human cytomegalovirus in peripheral blood leukocytes of immunocompromised viraemic patients. J Gen Virol. 1992 Feb;73(Pt 2):437–442. doi: 10.1099/0022-1317-73-2-437. [DOI] [PubMed] [Google Scholar]
  21. Reynolds D. W., Stagno S., Hosty T. S., Tiller M., Alford C. A., Jr Maternal cytomegalovirus excretion and perinatal infection. N Engl J Med. 1973 Jul 5;289(1):1–5. doi: 10.1056/NEJM197307052890101. [DOI] [PubMed] [Google Scholar]
  22. Rice G. P., Schrier R. D., Oldstone M. B. Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6134–6138. doi: 10.1073/pnas.81.19.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rubin R. H. Impact of cytomegalovirus infection on organ transplant recipients. Rev Infect Dis. 1990 Sep-Oct;12 (Suppl 7):S754–S766. doi: 10.1093/clinids/12.supplement_7.s754. [DOI] [PubMed] [Google Scholar]
  24. Scott D. M., Rodgers B. C., Freeke C., Buiter J., Sissons J. G. Human cytomegalovirus and monocytes: limited infection and negligible immunosuppression in normal mononuclear cells infected in vitro with mycoplasma-free virus strains. J Gen Virol. 1989 Mar;70(Pt 3):685–694. doi: 10.1099/0022-1317-70-3-685. [DOI] [PubMed] [Google Scholar]
  25. Simmons P., Kaushansky K., Torok-Storb B. Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1386–1390. doi: 10.1073/pnas.87.4.1386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sinclair J. H., Baillie J., Bryant L. A., Taylor-Wiedeman J. A., Sissons J. G. Repression of human cytomegalovirus major immediate early gene expression in a monocytic cell line. J Gen Virol. 1992 Feb;73(Pt 2):433–435. doi: 10.1099/0022-1317-73-2-433. [DOI] [PubMed] [Google Scholar]
  27. Sing G. K., Ruscetti F. W. Preferential suppression of myelopoiesis in normal human bone marrow cells after in vitro challenge with human cytomegalovirus. Blood. 1990 May 15;75(10):1965–1973. [PubMed] [Google Scholar]
  28. Taylor-Wiedeman J., Hayhurst G. P., Sissons J. G., Sinclair J. H. Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals. J Gen Virol. 1993 Feb;74(Pt 2):265–268. doi: 10.1099/0022-1317-74-2-265. [DOI] [PubMed] [Google Scholar]
  29. Taylor-Wiedeman J., Sissons J. G., Borysiewicz L. K., Sinclair J. H. Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol. 1991 Sep;72(Pt 9):2059–2064. doi: 10.1099/0022-1317-72-9-2059. [DOI] [PubMed] [Google Scholar]
  30. Taylor-Wiedeman J., Sissons P., Sinclair J. Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol. 1994 Mar;68(3):1597–1604. doi: 10.1128/jvi.68.3.1597-1604.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weinshenker B. G., Wilton S., Rice G. P. Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol. 1988 Mar 1;140(5):1625–1631. [PubMed] [Google Scholar]
  32. Whitelaw D. M. Observations on human monocyte kinetics after pulse labeling. Cell Tissue Kinet. 1972 Jul;5(4):311–317. doi: 10.1111/j.1365-2184.1972.tb00369.x. [DOI] [PubMed] [Google Scholar]

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