Abstract
Although viremia is a hallmark of disseminated cytomegalovirus (CMV) infection, not all viremic patients have visceral organ CMV disease. We used blot hybridization with a cloned subgenomic probe to quantitate viral DNA in blood leukocytes of 60 viremic patients (25 with solid organ transplants, 20 with AIDS, and 15 marrow recipients) who had different clinical manifestations of CMV infection. The results are expressed as pg of viral DNA/10 micrograms of leukocyte DNA. Patients with AIDS or with solid organ transplants who had CMV visceral organ disease had the largest amounts of viral DNA in their granulocytes (median 632 and 237 pg, respectively). These amounts were significantly greater than those in similar viremic patients without CMV visceral disease (17 and 21 pg; P < 0.005 and 0.002, respectively). All patients in the study with > 150 pg of CMV DNA in their granulocytes had visceral CMV disease. The amounts of viral DNA in granulocytes of AIDS and organ transplant patients with CMV retinitis were low (median 22 pg). Marrow transplant patients were unique in that the amounts of CMV DNA in granulocytes were low whether CMV visceral organ disease was present (17 pg) or absent (14 pg). We conclude that high levels of circulating CMV DNA in viremic AIDS and solid organ transplant patients reflect viral involvement of visceral organs but not the retina. In marrow recipients, the severity of CMV disease, even when fatal, is not reflected quantitatively in peripheral blood leukocytes.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnfred J., Nielsen C. M., Spencer E. S., Andersen H. K. A prospective study on infection with cytomegalovirus in renal allograft recipients immunosuppressed with cyclosporine A and low dose prednisone. Scand J Infect Dis. 1987;19(3):297–302. doi: 10.3109/00365548709018474. [DOI] [PubMed] [Google Scholar]
- Betts R. F. Cytomegalovirus infection in transplant patients. Prog Med Virol. 1982;28:44–64. [PubMed] [Google Scholar]
- Carney W. P., Iacoviello V., Hirsch M. S. Functional properties of T lymphocytes and their subsets in cytomegalovirus mononucleosis. J Immunol. 1983 Jan;130(1):390–393. [PubMed] [Google Scholar]
- Carney W. P., Rubin R. H., Hoffman R. A., Hansen W. P., Healey K., Hirsch M. S. Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis. J Immunol. 1981 Jun;126(6):2114–2116. [PubMed] [Google Scholar]
- Casareale D., Fiala M., Chang C. M., Cone L. A., Mocarski E. S. Cytomegalovirus enhances lysis of HIV-infected T lymphoblasts. Int J Cancer. 1989 Jul 15;44(1):124–130. doi: 10.1002/ijc.2910440122. [DOI] [PubMed] [Google Scholar]
- Cheeseman S. H., Rubin R. H., Stewart J. A., Tolkoff-Rubin N. E., Cosimi A. B., Cantell K., Gilbert J., Winkle S., Herrin J. T., Black P. H. Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections. N Engl J Med. 1979 Jun 14;300(24):1345–1349. doi: 10.1056/NEJM197906143002401. [DOI] [PubMed] [Google Scholar]
- Cox F., Hughes W. T. Cytomegaloviremia in children with acute lymphocytic leukemia. J Pediatr. 1975 Aug;87(2):190–194. doi: 10.1016/s0022-3476(75)80577-4. [DOI] [PubMed] [Google Scholar]
- Dankner W. M., McCutchan J. A., Richman D. D., Hirata K., Spector S. A. Localization of human cytomegalovirus in peripheral blood leukocytes by in situ hybridization. J Infect Dis. 1990 Jan;161(1):31–36. doi: 10.1093/infdis/161.1.31. [DOI] [PubMed] [Google Scholar]
- Davis M. G., Kenney S. C., Kamine J., Pagano J. S., Huang E. S. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8642–8646. doi: 10.1073/pnas.84.23.8642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dummer J. S., Hardy A., Poorsattar A., Ho M. Early infections in kidney, heart, and liver transplant recipients on cyclosporine. Transplantation. 1983 Sep;36(3):259–267. doi: 10.1097/00007890-198309000-00007. [DOI] [PubMed] [Google Scholar]
- Dummer J. S., White L. T., Ho M., Griffith B. P., Hardesty R. L., Bahnson H. T. Morbidity of cytomegalovirus infection in recipients of heart or heart-lung transplants who received cyclosporine. J Infect Dis. 1985 Dec;152(6):1182–1191. doi: 10.1093/infdis/152.6.1182. [DOI] [PubMed] [Google Scholar]
- Fiala M., Chatterjee S. N., Carson S., Poolsawat S., Heiner D. C., Saxon A., Guze L. B. Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes. Am J Ophthalmol. 1977 Oct;84(4):567–573. doi: 10.1016/0002-9394(77)90454-8. [DOI] [PubMed] [Google Scholar]
- Fiala M., Cone L. A., Chang C. M., Mocarski E. S. Cytomegalovirus viremia increases with progressive immune deficiency in patients infected with HTLV-III. AIDS Res. 1986 Summer;2(3):175–181. doi: 10.1089/aid.1.1986.2.175. [DOI] [PubMed] [Google Scholar]
- Fiala M., Payne J. E., Berne T. V., Moore T. C., Henle W., Montgomerie J. Z., Chatterjee S. N., Guze L. B. Epidemiology of cytomegalovirus infection after transplantation and immunosuppression. J Infect Dis. 1975 Oct;132(4):421–433. doi: 10.1093/infdis/132.4.421. [DOI] [PubMed] [Google Scholar]
- Gadler H., Tillegård A., Groth C. G. Studies of cytomegalovirus infection in renal allograft recipients. Scand J Infect Dis. 1982;14(2):81–87. doi: 10.3109/inf.1982.14.issue-2.01. [DOI] [PubMed] [Google Scholar]
- Gerna G., Parea M., Percivalle E., Zipeto D., Silini E., Barbarini G., Milanesi G. Human cytomegalovirus viraemia in HIV-1-seropositive patients at various clinical stages of infection. AIDS. 1990 Oct;4(10):1027–1031. doi: 10.1097/00002030-199010000-00014. [DOI] [PubMed] [Google Scholar]
- Glenn J. Cytomegalovirus infections following renal transplantation. Rev Infect Dis. 1981 Nov-Dec;3(6):1151–1178. doi: 10.1093/clinids/3.6.1151. [DOI] [PubMed] [Google Scholar]
- Grundy J. E., Shanley J. D., Griffiths P. D. Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition? Lancet. 1987 Oct 31;2(8566):996–999. doi: 10.1016/s0140-6736(87)92560-8. [DOI] [PubMed] [Google Scholar]
- Grundy J. E., Shanley J. D., Shearer G. M. Augmentation of graft-versus-host reaction by cytomegalovirus infection resulting in interstitial pneumonitis. Transplantation. 1985 May;39(5):548–553. doi: 10.1097/00007890-198505000-00018. [DOI] [PubMed] [Google Scholar]
- Hawley D. A., Schaefer J. F., Schulz D. M., Muller J. Cytomegalovirus encephalitis in acquired immunodeficiency syndrome. Am J Clin Pathol. 1983 Dec;80(6):874–877. doi: 10.1093/ajcp/80.6.874. [DOI] [PubMed] [Google Scholar]
- Hirsch M. S. Cytomegalovirus and its role in the pathogenesis of acquired immunodeficiency syndrome. Transplant Proc. 1991 Jun;23(3 Suppl 3):118-21, discussion 121. [PubMed] [Google Scholar]
- Ho W. Z., Harouse J. M., Rando R. F., Gönczöl E., Srinivasan A., Plotkin S. A. Reciprocal enhancement of gene expression and viral replication between human cytomegalovirus and human immunodeficiency virus type 1. J Gen Virol. 1990 Jan;71(Pt 1):97–103. doi: 10.1099/0022-1317-71-1-97. [DOI] [PubMed] [Google Scholar]
- Howell C. L., Miller M. J., Martin W. J. Comparison of rates of virus isolation from leukocyte populations separated from blood by conventional and Ficoll-Paque/Macrodex methods. J Clin Microbiol. 1979 Oct;10(4):533–537. doi: 10.1128/jcm.10.4.533-537.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hui A. N., Koss M. N., Meyer P. R. Necropsy findings in acquired immunodeficiency syndrome: a comparison of premortem diagnoses with postmortem findings. Hum Pathol. 1984 Jul;15(7):670–676. doi: 10.1016/s0046-8177(84)80293-2. [DOI] [PubMed] [Google Scholar]
- Jacobson M. A., Mills J. Serious cytomegalovirus disease in the acquired immunodeficiency syndrome (AIDS). Clinical findings, diagnosis, and treatment. Ann Intern Med. 1988 Apr;108(4):585–594. doi: 10.7326/0003-4819-108-4-585. [DOI] [PubMed] [Google Scholar]
- Levin M. J., Rinaldo C. R., Jr, Leary P. L., Zaia J. A., Hirsch M. S. Immune response to herpesvirus antigens in adults with acute cytomegaloviral mononucleosis. J Infect Dis. 1979 Dec;140(6):851–857. doi: 10.1093/infdis/140.6.851. [DOI] [PubMed] [Google Scholar]
- Martin D. C., Katzenstein D. A., Yu G. S., Jordan M. C. Cytomegalovirus viremia detected by molecular hybridization and electron microscopy. Ann Intern Med. 1984 Feb;100(2):222–225. doi: 10.7326/0003-4819-100-2-222. [DOI] [PubMed] [Google Scholar]
- Metselaar H. J., Balk A. H., Mochtar B., Rothbarth P. H., Weimar W. Cytomegalovirus seronegative heart transplant recipients. Prophylactic use of anti-CMV immunoglobulin. Chest. 1990 Feb;97(2):396–399. doi: 10.1378/chest.97.2.396. [DOI] [PubMed] [Google Scholar]
- Meyers J. D., Ljungman P., Fisher L. D. Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia. J Infect Dis. 1990 Aug;162(2):373–380. doi: 10.1093/infdis/162.2.373. [DOI] [PubMed] [Google Scholar]
- Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Hayward G. S., Pitha P. M. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408–7412. doi: 10.1073/pnas.84.21.7408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moskowitz L., Hensley G. T., Chan J. C., Adams K. Immediate causes of death in acquired immunodeficiency syndrome. Arch Pathol Lab Med. 1985 Aug;109(8):735–738. [PubMed] [Google Scholar]
- Neiman P. E., Reeves W., Ray G., Flournoy N., Lerner K. G., Sale G. E., Thomas E. D. A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts. J Infect Dis. 1977 Dec;136(6):754–767. doi: 10.1093/infdis/136.6.754. [DOI] [PubMed] [Google Scholar]
- Nelson J. A., Reynolds-Kohler C., Oldstone M. B., Wiley C. A. HIV and HCMV coinfect brain cells in patients with AIDS. Virology. 1988 Jul;165(1):286–290. doi: 10.1016/0042-6822(88)90685-x. [DOI] [PubMed] [Google Scholar]
- Nielsen S. L., Petito C. K., Urmacher C. D., Posner J. B. Subacute encephalitis in acquired immune deficiency syndrome: a postmortem study. Am J Clin Pathol. 1984 Dec;82(6):678–682. doi: 10.1093/ajcp/82.6.678. [DOI] [PubMed] [Google Scholar]
- Peterson P. K., Balfour H. H., Jr, Marker S. C., Fryd D. S., Howard R. J., Simmons R. L. Cytomegalovirus disease in renal allograft recipients: a prospective study of the clinical features, risk factors and impact on renal transplantation. Medicine (Baltimore) 1980 Jul;59(4):283–300. [PubMed] [Google Scholar]
- Pollard R. B., Egbert P. R., Gallagher J. G., Merigan T. C. Cytomegalovirus retinitis in immunosuppressed hosts. I. Natural history and effects of treatment with adenine arabinoside. Ann Intern Med. 1980 Nov;93(5):655–664. doi: 10.7326/0003-4819-93-5-655. [DOI] [PubMed] [Google Scholar]
- Pomerantz R. J., Kuritzkes D. R., de la Monte S. M., Rota T. R., Baker A. S., Albert D., Bor D. H., Feldman E. L., Schooley R. T., Hirsch M. S. Infection of the retina by human immunodeficiency virus type I. N Engl J Med. 1987 Dec 24;317(26):1643–1647. doi: 10.1056/NEJM198712243172607. [DOI] [PubMed] [Google Scholar]
- Quinnan G. V., Jr, Masur H., Rook A. H., Armstrong G., Frederick W. R., Epstein J., Manischewitz J. F., Macher A. M., Jackson L., Ames J. Herpesvirus infections in the acquired immune deficiency syndrome. JAMA. 1984 Jul 6;252(1):72–77. [PubMed] [Google Scholar]
- Reichert C. M., O'Leary T. J., Levens D. L., Simrell C. R., Macher A. M. Autopsy pathology in the acquired immune deficiency syndrome. Am J Pathol. 1983 Sep;112(3):357–382. [PMC free article] [PubMed] [Google Scholar]
- Richardson W. P., Colvin R. B., Cheeseman S. H., Tolkoff-Rubin N. E., Herrin J. T., Cosimi A. B., Collins A. B., Hirsch M. S., McCluskey R. T., Russell P. S. Glomerulopathy associated with cytomegalovirus viremia in renal allografts. N Engl J Med. 1981 Jul 9;305(2):57–63. doi: 10.1056/NEJM198107093050201. [DOI] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Rinaldo C. R., Jr, Black P. H., Hirsch M. S. Interaction of cytomegalovirus with leukocytes from patients with mononucleosis due to cytomegalovirus. J Infect Dis. 1977 Nov;136(5):667–678. doi: 10.1093/infdis/136.5.667. [DOI] [PubMed] [Google Scholar]
- Rinaldo C. R., Jr, Carney W. P., Richter B. S., Black P. H., Hirsch M. S. Mechanisms of immunosuppression in cytomegaloviral mononucleosis. J Infect Dis. 1980 Apr;141(4):488–495. doi: 10.1093/infdis/141.4.488. [DOI] [PubMed] [Google Scholar]
- Rubin R. H., Cosimi A. B., Tolkoff-Rubin N. E., Russell P. S., Hirsch M. S. Infectious disease syndromes attributable to cytomegalovirus and their significance among renal transplant recipients. Transplantation. 1977 Dec;24(6):458–464. doi: 10.1097/00007890-197712000-00010. [DOI] [PubMed] [Google Scholar]
- Salmon D., Lacassin F., Harzic M., Leport C., Perronne C., Bricaire F., Brun-Vezinet F., Vilde J. L. Predictive value of cytomegalovirus viraemia for the occurrence of CMV organ involvement in AIDS. J Med Virol. 1990 Nov;32(3):160–163. doi: 10.1002/jmv.1890320306. [DOI] [PubMed] [Google Scholar]
- Saltzman R. L., Quirk M. R., Jordan M. C. Disseminated cytomegalovirus infection. Molecular analysis of virus and leukocyte interactions in viremia. J Clin Invest. 1988 Jan;81(1):75–81. doi: 10.1172/JCI113313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saltzman R. L., Quirk M. R., Mariash C. N., Jordan M. C. Quantitation of cytomegalovirus DNA by blot hybridization in blood leukocytes of viremic patients. J Virol Methods. 1990 Oct;30(1):67–77. doi: 10.1016/0166-0934(90)90044-g. [DOI] [PubMed] [Google Scholar]
- Schmidt G. M., Horak D. A., Niland J. C., Duncan S. R., Forman S. J., Zaia J. A. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group. N Engl J Med. 1991 Apr 11;324(15):1005–1011. doi: 10.1056/NEJM199104113241501. [DOI] [PubMed] [Google Scholar]
- Shanley J. D., Pomeroy C., Via C. S., Shearer G. M. Interstitial pneumonitis during murine cytomegalovirus infection and graft-versus-host reaction: effect of ganciclovir therapy. J Infect Dis. 1988 Dec;158(6):1391–1394. doi: 10.1093/infdis/158.6.1391. [DOI] [PubMed] [Google Scholar]
- Shanley J. D., Via C. S., Sharrow S. O., Shearer G. M. Interstitial pneumonitis during murine cytomegalovirus infection and graft-versus-host reaction. Characterization of bronchoalveolar lavage cells. Transplantation. 1987 Nov;44(5):658–662. [PubMed] [Google Scholar]
- Shaw G. M., Harper M. E., Hahn B. H., Epstein L. G., Gajdusek D. C., Price R. W., Navia B. A., Petito C. K., O'Hara C. J., Groopman J. E. HTLV-III infection in brains of children and adults with AIDS encephalopathy. Science. 1985 Jan 11;227(4683):177–182. doi: 10.1126/science.2981429. [DOI] [PubMed] [Google Scholar]
- Shepp D. H., Dandliker P. S., de Miranda P., Burnette T. C., Cederberg D. M., Kirk L. E., Meyers J. D. Activity of 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine in the treatment of cytomegalovirus pneumonia. Ann Intern Med. 1985 Sep;103(3):368–373. doi: 10.7326/0003-4819-103-3-368. [DOI] [PubMed] [Google Scholar]
- Simmons R. L., Matas A. J., Rattazzi L. C., Balfour H. H., Jr, Howard J. R., Najarian J. S. Clinical characteristics of the lethal cytomegalovirus infection following renal transplantation. Surgery. 1977 Nov;82(5):537–546. [PubMed] [Google Scholar]
- Skolnik P. R., Kosloff B. R., Hirsch M. S. Bidirectional interactions between human immunodeficiency virus type 1 and cytomegalovirus. J Infect Dis. 1988 Mar;157(3):508–514. doi: 10.1093/infdis/157.3.508. [DOI] [PubMed] [Google Scholar]
- Skolnik P. R., Pomerantz R. J., de la Monte S. M., Lee S. F., Hsiung G. D., Foos R. Y., Cowan G. M., Kosloff B. R., Hirsch M. S., Pepose J. S. Dual infection of retina with human immunodeficiency virus type 1 and cytomegalovirus. Am J Ophthalmol. 1989 Apr 15;107(4):361–372. doi: 10.1016/0002-9394(89)90659-4. [DOI] [PubMed] [Google Scholar]
- Spector S. A., Rua J. A., Spector D. H., McMillan R. Detection of human cytomegalovirus in clinical specimens by DNA-DNA hybridization. J Infect Dis. 1984 Jul;150(1):121–126. doi: 10.1093/infdis/150.1.121. [DOI] [PubMed] [Google Scholar]
- Turtinen L. W., Saltzman R., Jordan M. C., Haase A. T. Interactions of human cytomegalovirus with leukocytes in vivo: analysis by in situ hybridization. Microb Pathog. 1987 Oct;3(4):287–297. doi: 10.1016/0882-4010(87)90062-3. [DOI] [PubMed] [Google Scholar]
- Vilmer E., Mazeron M. C., Rabian C., Azogui O., Devergie A., Perol Y., Gluckman E. Clinical significance of cytomegalovirus viremia in bone marrow transplantation. Transplantation. 1985 Jul;40(1):30–35. doi: 10.1097/00007890-198507000-00007. [DOI] [PubMed] [Google Scholar]
- Welch K., Finkbeiner W., Alpers C. E., Blumenfeld W., Davis R. L., Smuckler E. A., Beckstead J. H. Autopsy findings in the acquired immune deficiency syndrome. JAMA. 1984 Sep 7;252(9):1152–1159. [PubMed] [Google Scholar]
- Winston D. J., Gale R. P., Meyer D. V., Young L. S. Infectious complications of human bone marrow transplantation. Medicine (Baltimore) 1979 Jan;58(1):1–31. doi: 10.1097/00005792-197901000-00001. [DOI] [PubMed] [Google Scholar]
- Zaia J. A., Forman S. J., Gallagher M. T., Vanderwal-Urbina E., Blume K. G. Prolonged human cytomegalovirus viremia following bone marrow transplantation. Transplantation. 1984 Mar;37(3):315–317. doi: 10.1097/00007890-198403000-00021. [DOI] [PubMed] [Google Scholar]