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Vol. 42, No. 5-6, 1999
Issue release date: September–December 1999 (February 2000)
Intervirology 1999;42:308–313
(DOI:10.1159/000053965)

Human Cytomegalovirus Reactivation in Bone-Marrow-Derived Granulocyte/Monocyte Progenitor Cells and Mature Monocytes

Prösch S.a · Döcke W-D.b · Reinke P.c · Volk H-D.b · Krüger D.H.a
Departments of aVirology, bMedical Immunology and cNephrology/Internal Intensive Care Medicine, School of Medicine (Charité), Humboldt University, Berlin, Germany
email Corresponding Author

Abstract

Monocyte/granulocyte progenitor cells of the bone marrow are a major site of human cytomegalovirus (HCMV) latency. The mechanisms of establishment and maintenance of HCMV latency are still unknown. Reactivation of the latent virus in bone-marrow-derived progenitor cells has been demonstrated in vitro and suggested to occur also in vivo. Clinical studies have shown that reactivation is a rather frequent event not only in immunosuppressed but also in nonimmunosuppressed patients and in healthy blood donors. At least three independent mechanisms of virus reactivation are discussed: systemic inflammation connected with strong tumor necrosis factor alpha release; application of cAMP-elevating drugs, and highly stressful events associated with increased plasma catecholamine levels.


 goto top of outline Key Words

  • Human cytomegalovirus
  • Virus reactivation
  • Monocyte/granulocyte progenitor cells
  • Systemic inflammation
  • TNF-α
  • Stress
  • cAMP

 goto top of outline Abstract

Monocyte/granulocyte progenitor cells of the bone marrow are a major site of human cytomegalovirus (HCMV) latency. The mechanisms of establishment and maintenance of HCMV latency are still unknown. Reactivation of the latent virus in bone-marrow-derived progenitor cells has been demonstrated in vitro and suggested to occur also in vivo. Clinical studies have shown that reactivation is a rather frequent event not only in immunosuppressed but also in nonimmunosuppressed patients and in healthy blood donors. At least three independent mechanisms of virus reactivation are discussed: systemic inflammation connected with strong tumor necrosis factor alpha release; application of cAMP-elevating drugs, and highly stressful events associated with increased plasma catecholamine levels.

Copyright © 2000 S. Karger AG, Basel


 goto top of outline References
  1. Stanier P, Kitchen AD, Taylor DL, Tyms AS: Detection of human cytomegalovirus in peripheral mononuclear cells and urine samples using PCR. Mol Cell Probes 1992;6:51–58.
  2. Bevan IS, Daw RA, Day PJ, Ala FA, Walker MR: Polymerase chain reaction for detection of human cytomegalovirus infection in a blood donor population. Br J Haematol 1991;78:94–99.
  3. Smith KL, Kulski JK, Cobain T, Dunstan RA: Detection of cytomegalovirus in blood donors by the polymerase chain reaction. Transfusion 1993;33:497–503.
  4. Döcke WD, Prösch S, Fietze E, Kimel V, Zuckermann H, Kluge C, Syrbe U, Krüger DH, von Baehr R, Volk HD: Cytomegalovirus reactivation and tumor necrosis factor. Lancet 1994;343:268–269.
  5. Söderberg-Naucler C, Fish KN, Nelson JA: Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell 1997;91:119–126.
  6. Larsson S. Söderberg-Naucler C, Wang FZ, Möller E: Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time. Transfusion 1998;38:271–278.
  7. Taylor-Wiedeman J, Sissons JG, Borysiewicz LK, Sinclair JH: Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol 1991;72:2059–2064.
  8. Taylor-Wiedeman J, Hayhurst GP, Sissons JG, Sinclair JH: Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals. J Gen Virol 1993;74:265–268.

    External Resources

  9. Mendelson M, Monard S, Sissons P, Sinclair J: Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol 1996;77:3099–3102.
  10. Kondo K, Xu J. Mocarski ES: Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci USA 1996;93:11137–11142.
  11. Sindre H, Tjoonnfjord GE, Rollag H, Ranneberg-Nilsen T, Veiby OP, Beck S, Degre M, Hestdal K: Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells. Blood 1996;88:4526–4533.
  12. Slobedman B, Mocarski ES: Quantitative analysis of latent human cytomegalovirus. J Virol 1999;73:4806–4812.

    External Resources

  13. Bolovan-Fritts CA, Mocarski ES, Wiedeman JA: Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood 1999;93:394–398.
  14. Taylor-Wiedeman J, Sissons P, Sinclair J: Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol 1994;68:1597–1604.

    External Resources

  15. Kondo K, Kaneshima H, Mocarski ES: Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. Proc Natl Acad Sci USA 1994;91:11879–11883.

    External Resources

  16. Kondo K, Mocarski ES: Cytomegalovirus latency and latency-specific transcription in hematopoietic progenitors. Scand J Infect Dis Suppl 1995;99:63–67.
  17. Minton EJ, Tysoe C, Sinclair JH, Sissons JG: Human cytomegalovirus infection of the monocyte/macrophage lineage in bone marrow. J Virol 1994;68:4017–4021.

    External Resources

  18. Hahn G, Jores R, Mocarski ES: Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci USA 1998;95:3937–3942.
  19. Mitchell BM, Leung A, Stevens JG: Murine cytomegalovirus DNA in peripheral blood of latently infected mice is detectable only on monocytes and polymorphonuclear leukocytes. Virology 1996;223:198–207.

    External Resources

  20. Koffron AJ, Hummel M, Patterson BK, Yan S, Kaufman DB, Fryer JP, Stuart FP, Abecassis MI: Cellular localization of latent murine cytomegalovirus. J Virol 1998;72:95–103.

    External Resources

  21. Henry S: Induction of MCMV gene expression in latently infected macrophage progenitor cells by maturation stimuli (abstract). J Clin Virol 1999;12:98.
  22. Mutimer D, Mirza D, Shaw K, O’Donnell K, Elias E: Enhanced (cytomegalovirus) viral replication associated with septic bacterial complications in liver transplant recipients. Transplantation 1997;63:1411–1415.

    External Resources

  23. Kutza AS, Muhl E, Hackstien H, Kirchner H, Bein G: High incidence of active cytomegalovirus infection among septic patients. Clin Infect Dis 1998;26:1076–1082.

    External Resources

  24. Machens A, Bloechle C, Achilles EG, Bause HW, Izbicki JR: Toxic megacolon caused by cytomegalovirus colitis in a multiply injured patient. J Trauma 1996;40:644–646.

    External Resources

  25. Stephan P, Meharzi D, Ricci S, Fajac A, Clergue F, Bernaudin JF: Evaluation by polymerase chain reaction of cytomegalovirus reactivation in intensive care patients under mechanical ventilation. Intensive Care Med 1996;22:1244–1249.
  26. Asadullah K, Prösch S, Audring H, Büttnerova L, Volk HD, Sterry W, Döcke WD: A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: An association with systemic tumor necrosis factor α overexpression. Br J Dermatol 1999;141:94–102.
  27. Toro AI, Ossa J: PCR activity of CMV in healthy CMV-seropositive individuals: Does latency need redefinition? Res Virol 1996;147:233–238.

    External Resources

  28. Kern F, Surel IP, Brock C, Freistedt B, Radtke H, Scheffold A, Blasczyk R, Reinke P, Schneider-Mergener J, Radbruch A, Walden P, Volk HD: T-cell epitope mapping by flow cytometry. Nat Med 1998;4:975–978.

    External Resources

  29. Singh N, Dummer JS, Kusne S, Breinig MK, Armstrong JA, Makowka L, Starzl TE, Ho M: Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: Transmission by donated organ and the effect of OKT3 antibodies. J Infect Dis 1988;158:124–131.
  30. Hooks MA, Perlino CA, Henderson JM, Millikan WJ Jr, Kutner MH: Prevalence of invasive cytomegalovirus disease with administration of muromanab CD-3 in patients undergoing orthotopic liver transplantation. Ann Pharmacother 1992;26:617–620.
  31. Hibberd PL, Tolkoff-Rubin NE, Cosimi AB, Schooley RT, Isaacson D, Doran M, Delvecchio A, Delmonico FL, Auchincloss H Jr, Rubin RH: Symptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipients treated with OKT3. Transplantation 1992;53:68–72.

    External Resources

  32. Paya CV, Wiesner RH, Hermanns PE, Larson-Keller JJ, Ilstrup DM, Krom RA, Rettke S, Smith TF: Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: A prospective multivariate time-dependent analysis. J Hepatol 1993;18:185–195.
  33. Fietze E, Prösch S, Reinke P, Stein J, Döcke WD, Staffa G, Loening S, Devaux S, Emmrich F, von Baehr R, Krüger DH, Volk HD: Cytomegalovirus infection in transplant recipients: The role of tumor necrosis factor. Transplantation 1994;58:675–680.

    External Resources

  34. Krogsgaard K, Boesgaard S, Aldershvile J, Arendrup H, Mortensen SA, Petterson G: Cytomegalovirus infection rate among heart transplant patients in relation to the potency of antithymocyte immunoglobulin induction therapy. Copenhagen Heart Transplant Group. Scand J Infect Dis 1994;26:239–247.
  35. Portela D, Patel R, Larson-Keller JJ, Ilstrup DM, Wiesner RH, Steers JL, Krom RA, Paya CV: OKT3 treatment for allograft rejection is a risk factor for cytomegalovirus disease in liver transplantation. J Infect Dis 1995;171:1014–1018.

    External Resources

  36. Prösch S, Volk HD, Reinke P, Pioch K, Döcke WD, Krüger DH: Human cytomegalovirus infection in transplant recipients: Role of TNFα for reactivation and replication of human cytomegalovirus; in Scholz M, Rabenau HF, Doerr HW, Cinatl J Jr (eds): CMV-Related Immunopathology. Monogr Virol. Basel, Karger, 1998, vol 21, pp 29–42.
  37. Humar A, St Loius P, Mazzulli T, McGeer A, Lipton J, Messner H, MacDonald KS: Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients. J Infect Dis 1999;179:484–488.
  38. Koffron A, Varghese T, Hummel M, Yan S, Kaufman D, Fryer J, Leventhal J, Stuart F, Abecassis M: Immunosuppression is not required for reactivation of latent murine cytomegalovirus. Transplant Proc 1999;31:1395–1396.

    External Resources

  39. Stein J, Volk HD, Liebenthal C, Krüger DH, Prösch S: Tumor necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells. J Gen Virol 1993;74:2333–2338.
  40. Iskenderian AC, Huang L, Reilly A, Stenberg RM, Anders DG: Four of eleven loci required for transition complementation of human cytomegalovirus DNA replication cooperate to activate expression of replication genes. J Virol 1996;70:383–392.

    External Resources

  41. Mocarski ES, Kemble GW, Lyle JM, Greaves RF: A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is replication defective due to a failure in autoregulation. Proc Natl Acad Sci USA 1996;93:11321–11326.
  42. Greaves RF, Mocarski ES: Defective growth correlates with reduced accumulation of a viral DNA replication protein after low-multiplicity infection by a human cytomegalovirus ie1 mutant. J Virol 1998;72:366–379.

    External Resources

  43. Prösch S, Staak K, Stein J, Liebenthal C, Stamminger T, Volk HD, Krüger DH: Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFα is mediated via induction of NF-κB. Virology 1995;208:197–206.
  44. Söderberg-Naucler C, Fish KN, Nelson JA: Interferon-γ and tumor necrosis factor-α specifically induce formation of cytomegalovirus-permissive monocyte-derived macrophages that are refractory to the antiviral activity of these cytokines. J Clin Invest 1997;100:3154–3163.
  45. Staak K, Prösch S, Stein J, Priemer C, Ewert R, Döcke WD, Krüger DH, Volk HD, Reinke P: Pentoxifylline promotes replication of cytomegalovirus in vivo and in vitro. Blood 1997;89:3682–3690.
  46. Steiner I: Human herpes viruses latent infection in the nervous system. Immunol Rev 1996;152:157–173.

    External Resources

  47. Turner SL, Jenkins FJ: The role of herpes simplex virus in neuroscience. J Neurovirol 1997;3:110–125.

    External Resources

  48. Paterson DL, Steplefeldt WH, Wagener MM, Gayowski T, Marino IR, Singh N: Intraoperative hypothermia is an independent risk factor for early cytomegalovirus infection in liver transplant recipients. Transplantation 1999;27:1151–1155.
  49. Przepiorka D, Ippoliti C, Panina A, Goodrich J, Giralt S, van Besien K, Mehra R, Deisseroth AB, Andersson B, Luna M et al: Ganciclovir three times per week is not adequate to prevent cytomegalovirus reactivation after T-cell-depleted marrow transplantation. Bone Marrow Transplant 1994;13:461–464.

    External Resources

  50. Winston DJ, Imagawa DK, Holt CD, Kaldas F, Shaked A, Busuttil RW: Long-term ganciclovir prophylaxis eliminates serious cytomegalovirus disease in liver transplant recipients receiving OKT3 therapy for rejection. Transplantation 1995;60:1357–1360.

    External Resources

  51. Gomez E, de Ona M, Aguado S, Tejada F, Nunez M, Portal C, Diaz-Corte C, Sanchez E, Ortega F, Alvarez-Grande J: Cytomegalovirus preemptive therapy with ganciclovir in renal transplant patients treated with OKT3. Nephron 1996;74:367–372.
  52. Canpolat C, Culbert S, Gardner M, Whimbey E, Tarrand J, Chan KW: Ganciclovir prophylaxis for cytomegalovirus infection in pediatric allogenic bone marrow transplant recipients. Bone Marow Transplant 1996;17:589–593.
  53. Grundy JE: Current antiviral therapy fails to prevent the pro-inflammatory effects of cytomegalovirus infection, whilst rendering infected cells relatively resistant to immune attack; in Scholz M, Rabenau HF, Doerr HW, Cinatl J Jr (eds): CMV-Related Immunopathology. Monogr Virol. Basel, Karger, 1998, vol 21, pp 67–89.

 goto top of outline Author Contacts

PD Dr. Susanna Prösch
Institut für Virologie, Universitätsklinikum Charité
Campus Charité-Mitte, Humboldt-Universität
Schumannstrasse 20/21, D–10098 Berlin (Germany)
Tel. +49 30 2802 3117, Fax +49 30 2802 2180, E-Mail susanna.proesch@charite.de


 goto top of outline Article Information

Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 0, Number of References : 53


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986–1990); M.J. Buchmeier and C.R. Howard (1991–1993)

Vol. 42, No. 5-6, Year 1999 (Cover Date: September-December 1999 (Released February 2000))

Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300–5526 (print), 1423–0100 (Online)

For additional information: http://www.karger.com/journals/int


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Monocyte/granulocyte progenitor cells of the bone marrow are a major site of human cytomegalovirus (HCMV) latency. The mechanisms of establishment and maintenance of HCMV latency are still unknown. Reactivation of the latent virus in bone-marrow-derived progenitor cells has been demonstrated in vitro and suggested to occur also in vivo. Clinical studies have shown that reactivation is a rather frequent event not only in immunosuppressed but also in nonimmunosuppressed patients and in healthy blood donors. At least three independent mechanisms of virus reactivation are discussed: systemic inflammation connected with strong tumor necrosis factor alpha release; application of cAMP-elevating drugs, and highly stressful events associated with increased plasma catecholamine levels.



 goto top of outline Author Contacts

PD Dr. Susanna Prösch
Institut für Virologie, Universitätsklinikum Charité
Campus Charité-Mitte, Humboldt-Universität
Schumannstrasse 20/21, D–10098 Berlin (Germany)
Tel. +49 30 2802 3117, Fax +49 30 2802 2180, E-Mail susanna.proesch@charite.de


 goto top of outline Article Information

Number of Print Pages : 6
Number of Figures : 1, Number of Tables : 0, Number of References : 53


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986–1990); M.J. Buchmeier and C.R. Howard (1991–1993)

Vol. 42, No. 5-6, Year 1999 (Cover Date: September-December 1999 (Released February 2000))

Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300–5526 (print), 1423–0100 (Online)

For additional information: http://www.karger.com/journals/int


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Stanier P, Kitchen AD, Taylor DL, Tyms AS: Detection of human cytomegalovirus in peripheral mononuclear cells and urine samples using PCR. Mol Cell Probes 1992;6:51–58.
  2. Bevan IS, Daw RA, Day PJ, Ala FA, Walker MR: Polymerase chain reaction for detection of human cytomegalovirus infection in a blood donor population. Br J Haematol 1991;78:94–99.
  3. Smith KL, Kulski JK, Cobain T, Dunstan RA: Detection of cytomegalovirus in blood donors by the polymerase chain reaction. Transfusion 1993;33:497–503.
  4. Döcke WD, Prösch S, Fietze E, Kimel V, Zuckermann H, Kluge C, Syrbe U, Krüger DH, von Baehr R, Volk HD: Cytomegalovirus reactivation and tumor necrosis factor. Lancet 1994;343:268–269.
  5. Söderberg-Naucler C, Fish KN, Nelson JA: Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell 1997;91:119–126.
  6. Larsson S. Söderberg-Naucler C, Wang FZ, Möller E: Cytomegalovirus DNA can be detected in peripheral blood mononuclear cells from all seropositive and most seronegative healthy blood donors over time. Transfusion 1998;38:271–278.
  7. Taylor-Wiedeman J, Sissons JG, Borysiewicz LK, Sinclair JH: Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol 1991;72:2059–2064.
  8. Taylor-Wiedeman J, Hayhurst GP, Sissons JG, Sinclair JH: Polymorphonuclear cells are not sites of persistence of human cytomegalovirus in healthy individuals. J Gen Virol 1993;74:265–268.

    External Resources

  9. Mendelson M, Monard S, Sissons P, Sinclair J: Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol 1996;77:3099–3102.
  10. Kondo K, Xu J. Mocarski ES: Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci USA 1996;93:11137–11142.
  11. Sindre H, Tjoonnfjord GE, Rollag H, Ranneberg-Nilsen T, Veiby OP, Beck S, Degre M, Hestdal K: Human cytomegalovirus suppression of and latency in early hematopoietic progenitor cells. Blood 1996;88:4526–4533.
  12. Slobedman B, Mocarski ES: Quantitative analysis of latent human cytomegalovirus. J Virol 1999;73:4806–4812.

    External Resources

  13. Bolovan-Fritts CA, Mocarski ES, Wiedeman JA: Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood 1999;93:394–398.
  14. Taylor-Wiedeman J, Sissons P, Sinclair J: Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers. J Virol 1994;68:1597–1604.

    External Resources

  15. Kondo K, Kaneshima H, Mocarski ES: Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. Proc Natl Acad Sci USA 1994;91:11879–11883.

    External Resources

  16. Kondo K, Mocarski ES: Cytomegalovirus latency and latency-specific transcription in hematopoietic progenitors. Scand J Infect Dis Suppl 1995;99:63–67.
  17. Minton EJ, Tysoe C, Sinclair JH, Sissons JG: Human cytomegalovirus infection of the monocyte/macrophage lineage in bone marrow. J Virol 1994;68:4017–4021.

    External Resources

  18. Hahn G, Jores R, Mocarski ES: Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci USA 1998;95:3937–3942.
  19. Mitchell BM, Leung A, Stevens JG: Murine cytomegalovirus DNA in peripheral blood of latently infected mice is detectable only on monocytes and polymorphonuclear leukocytes. Virology 1996;223:198–207.

    External Resources

  20. Koffron AJ, Hummel M, Patterson BK, Yan S, Kaufman DB, Fryer JP, Stuart FP, Abecassis MI: Cellular localization of latent murine cytomegalovirus. J Virol 1998;72:95–103.

    External Resources

  21. Henry S: Induction of MCMV gene expression in latently infected macrophage progenitor cells by maturation stimuli (abstract). J Clin Virol 1999;12:98.
  22. Mutimer D, Mirza D, Shaw K, O’Donnell K, Elias E: Enhanced (cytomegalovirus) viral replication associated with septic bacterial complications in liver transplant recipients. Transplantation 1997;63:1411–1415.

    External Resources

  23. Kutza AS, Muhl E, Hackstien H, Kirchner H, Bein G: High incidence of active cytomegalovirus infection among septic patients. Clin Infect Dis 1998;26:1076–1082.

    External Resources

  24. Machens A, Bloechle C, Achilles EG, Bause HW, Izbicki JR: Toxic megacolon caused by cytomegalovirus colitis in a multiply injured patient. J Trauma 1996;40:644–646.

    External Resources

  25. Stephan P, Meharzi D, Ricci S, Fajac A, Clergue F, Bernaudin JF: Evaluation by polymerase chain reaction of cytomegalovirus reactivation in intensive care patients under mechanical ventilation. Intensive Care Med 1996;22:1244–1249.
  26. Asadullah K, Prösch S, Audring H, Büttnerova L, Volk HD, Sterry W, Döcke WD: A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: An association with systemic tumor necrosis factor α overexpression. Br J Dermatol 1999;141:94–102.
  27. Toro AI, Ossa J: PCR activity of CMV in healthy CMV-seropositive individuals: Does latency need redefinition? Res Virol 1996;147:233–238.

    External Resources

  28. Kern F, Surel IP, Brock C, Freistedt B, Radtke H, Scheffold A, Blasczyk R, Reinke P, Schneider-Mergener J, Radbruch A, Walden P, Volk HD: T-cell epitope mapping by flow cytometry. Nat Med 1998;4:975–978.

    External Resources

  29. Singh N, Dummer JS, Kusne S, Breinig MK, Armstrong JA, Makowka L, Starzl TE, Ho M: Infections with cytomegalovirus and other herpesviruses in 121 liver transplant recipients: Transmission by donated organ and the effect of OKT3 antibodies. J Infect Dis 1988;158:124–131.
  30. Hooks MA, Perlino CA, Henderson JM, Millikan WJ Jr, Kutner MH: Prevalence of invasive cytomegalovirus disease with administration of muromanab CD-3 in patients undergoing orthotopic liver transplantation. Ann Pharmacother 1992;26:617–620.
  31. Hibberd PL, Tolkoff-Rubin NE, Cosimi AB, Schooley RT, Isaacson D, Doran M, Delvecchio A, Delmonico FL, Auchincloss H Jr, Rubin RH: Symptomatic cytomegalovirus disease in the cytomegalovirus antibody seropositive renal transplant recipients treated with OKT3. Transplantation 1992;53:68–72.

    External Resources

  32. Paya CV, Wiesner RH, Hermanns PE, Larson-Keller JJ, Ilstrup DM, Krom RA, Rettke S, Smith TF: Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: A prospective multivariate time-dependent analysis. J Hepatol 1993;18:185–195.
  33. Fietze E, Prösch S, Reinke P, Stein J, Döcke WD, Staffa G, Loening S, Devaux S, Emmrich F, von Baehr R, Krüger DH, Volk HD: Cytomegalovirus infection in transplant recipients: The role of tumor necrosis factor. Transplantation 1994;58:675–680.

    External Resources

  34. Krogsgaard K, Boesgaard S, Aldershvile J, Arendrup H, Mortensen SA, Petterson G: Cytomegalovirus infection rate among heart transplant patients in relation to the potency of antithymocyte immunoglobulin induction therapy. Copenhagen Heart Transplant Group. Scand J Infect Dis 1994;26:239–247.
  35. Portela D, Patel R, Larson-Keller JJ, Ilstrup DM, Wiesner RH, Steers JL, Krom RA, Paya CV: OKT3 treatment for allograft rejection is a risk factor for cytomegalovirus disease in liver transplantation. J Infect Dis 1995;171:1014–1018.

    External Resources

  36. Prösch S, Volk HD, Reinke P, Pioch K, Döcke WD, Krüger DH: Human cytomegalovirus infection in transplant recipients: Role of TNFα for reactivation and replication of human cytomegalovirus; in Scholz M, Rabenau HF, Doerr HW, Cinatl J Jr (eds): CMV-Related Immunopathology. Monogr Virol. Basel, Karger, 1998, vol 21, pp 29–42.
  37. Humar A, St Loius P, Mazzulli T, McGeer A, Lipton J, Messner H, MacDonald KS: Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients. J Infect Dis 1999;179:484–488.
  38. Koffron A, Varghese T, Hummel M, Yan S, Kaufman D, Fryer J, Leventhal J, Stuart F, Abecassis M: Immunosuppression is not required for reactivation of latent murine cytomegalovirus. Transplant Proc 1999;31:1395–1396.

    External Resources

  39. Stein J, Volk HD, Liebenthal C, Krüger DH, Prösch S: Tumor necrosis factor alpha stimulates the activity of the human cytomegalovirus major immediate early enhancer/promoter in immature monocytic cells. J Gen Virol 1993;74:2333–2338.
  40. Iskenderian AC, Huang L, Reilly A, Stenberg RM, Anders DG: Four of eleven loci required for transition complementation of human cytomegalovirus DNA replication cooperate to activate expression of replication genes. J Virol 1996;70:383–392.

    External Resources

  41. Mocarski ES, Kemble GW, Lyle JM, Greaves RF: A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is replication defective due to a failure in autoregulation. Proc Natl Acad Sci USA 1996;93:11321–11326.
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