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. 1988 Jun;131(3):490–496.

In situ hybridization for cytomegalovirus DNA in AIDS patients.

W C Keh 1, M A Gerber 1
PMCID: PMC1880704  PMID: 2837903

Abstract

Infection by cytomegalovirus (CMV) is a frequent cause of morbidity and mortality in patients with acquired immune deficiency syndrome (AIDS). The authors studied the distribution of CMV in 4 patients with AIDS using a commercially available, biotin-labeled CMV DNA probe for in situ hybridization and immunohistochemical staining for the detection of CMV antigen in formalin-fixed paraffin-embedded tissues. The sensitivity and specificity of the hybridization procedure was demonstrated by appropriate controls. The immunohistochemical test for the detection of CMV antigen in routine histologic sections was less sensitive than the in situ hybridization method. CMV DNA was detected not only in cytomegalic inclusion cells, but also in nuclei and cytoplasm of histologically normal-appearing cells such as endothelial cells, pneumocytes, hepatocytes, biliary epithelium, gastrointestinal epithelium, Langerhans islet cells, acinar and duct epithelium of pancreas, adrenal cortical and medullary cells, and prostate epithelium. In addition, CMV DNA, but not CMV antigen, was found in polymorphonuclear leukocytes. These cells may serve as intermediate host or reservoir of CMV and may transmit posttransfusion CMV infection. In situ hybridization on routine histologic sections with a biotinylated CMV DNA probe is a rapid, sensitive, and specific method for diagnostic and experimental pathology.

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Selected References

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

  1. Baskin G. B. Disseminated cytomegalovirus infection in immunodeficient rhesus monkeys. Am J Pathol. 1987 Nov;129(2):345–352. [PMC free article] [PubMed] [Google Scholar]
  2. Betts R. F. Cytomegalovirus infection in transplant patients. Prog Med Virol. 1982;28:44–64. [PubMed] [Google Scholar]
  3. Brigati D. J., Myerson D., Leary J. J., Spalholz B., Travis S. Z., Fong C. K., Hsiung G. D., Ward D. C. Detection of viral genomes in cultured cells and paraffin-embedded tissue sections using biotin-labeled hybridization probes. Virology. 1983 Apr 15;126(1):32–50. doi: 10.1016/0042-6822(83)90460-9. [DOI] [PubMed] [Google Scholar]
  4. Coleman D. V. Cytological diagnosis of virus-infected cells in Papanicolaou smears and its application in clinical practice. J Clin Pathol. 1979 Nov;32(11):1075–1089. doi: 10.1136/jcp.32.11.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dylewski J., Chou S., Merigan T. C. Absence of detectable IgM antibody during cytomegalovirus disease in patients with AIDS. N Engl J Med. 1983 Aug 25;309(8):493–493. doi: 10.1056/NEJM198308253090813. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Goldstein L. C., McDougall J., Hackman R., Meyers J. D., Thomas E. D., Nowinski R. C. Monoclonal antibodies to cytomegalovirus: rapid identification of clinical isolates and preliminary use in diagnosis of cytomegalovirus pneumonia. Infect Immun. 1982 Oct;38(1):273–281. doi: 10.1128/iai.38.1.273-281.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hackman R. C., Myerson D., Meyers J. D., Shulman H. M., Sale G. E., Goldstein L. C., Rastetter M., Flournoy N., Thomas E. D. Rapid diagnosis of cytomegaloviral pneumonia by tissue immunofluorescence with a murine monoclonal antibody. J Infect Dis. 1985 Feb;151(2):325–329. doi: 10.1093/infdis/151.2.325. [DOI] [PubMed] [Google Scholar]
  10. Hersman J., Meyers J. D., Thomas E. D., Buckner C. D., Clift R. The effect of granulocyte transfusions on the incidence of cytomegalovirus infection after allogeneic marrow transplantation. Ann Intern Med. 1982 Feb;96(2):149–152. doi: 10.7326/0003-4819-96-2-149. [DOI] [PubMed] [Google Scholar]
  11. Kangro H. O., Griffiths P. D., Huber T. J., Heath R. B. Specific IgM class antibody production following infection with cytomegalovirus. J Med Virol. 1982;10(3):203–212. doi: 10.1002/jmv.1890100306. [DOI] [PubMed] [Google Scholar]
  12. Löning T., Milde K., Foss H. D. In situ hybridization for the detection of cytomegalovirus (CMV) infection. Application of biotinylated CMV-DNA probes on paraffin-embedded specimens. Virchows Arch A Pathol Anat Histopathol. 1986;409(6):777–790. doi: 10.1007/BF00710763. [DOI] [PubMed] [Google Scholar]
  13. McDougall J. K., Myerson D., Beckmann A. M. Detection of viral DNA and RNA by in situ hybridization. J Histochem Cytochem. 1986 Jan;34(1):33–38. doi: 10.1177/34.1.3001177. [DOI] [PubMed] [Google Scholar]
  14. Meyers J. D., Flournoy N., Thomas E. D. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis. 1982 Nov-Dec;4(6):1119–1132. doi: 10.1093/clinids/4.6.1119. [DOI] [PubMed] [Google Scholar]
  15. Myerson D., Hackman R. C., Meyers J. D. Diagnosis of cytomegaloviral pneumonia by in situ hybridization. J Infect Dis. 1984 Aug;150(2):272–277. doi: 10.1093/infdis/150.2.272. [DOI] [PubMed] [Google Scholar]
  16. Myerson D., Hackman R. C., Nelson J. A., Ward D. C., McDougall J. K. Widespread presence of histologically occult cytomegalovirus. Hum Pathol. 1984 May;15(5):430–439. doi: 10.1016/s0046-8177(84)80076-3. [DOI] [PubMed] [Google Scholar]
  17. Naraqi S., Jackson G. G., Jonasson O., Rubenis M. Search for latent cytomegalovirus in renal allografts. Infect Immun. 1978 Feb;19(2):699–703. doi: 10.1128/iai.19.2.699-703.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Niedt G. W., Schinella R. A. Acquired immunodeficiency syndrome. Clinicopathologic study of 56 autopsies. Arch Pathol Lab Med. 1985 Aug;109(8):727–734. [PubMed] [Google Scholar]
  19. Panjwani D. D., Ball M. G., Berry N. J., Wimperis J. Z., Blacklock H. A., Prentice H. G., Hoffbrand A. V., Griffiths P. D. Virological and serological diagnosis of cytomegalovirus infection in bone marrow allograft recipients. J Med Virol. 1985 Aug;16(4):357–365. doi: 10.1002/jmv.1890160409. [DOI] [PubMed] [Google Scholar]
  20. Przepiorka D., Myerson D. A single-step silver enhancement method permitting rapid diagnosis of cytomegalovirus infection in formalin-fixed, paraffin-embedded tissue sections by in situ hybridization and immunoperoxidase detection. J Histochem Cytochem. 1986 Dec;34(12):1731–1734. doi: 10.1177/34.12.3023477. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Schrier R. D., Nelson J. A., Oldstone M. B. Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science. 1985 Nov 29;230(4729):1048–1051. doi: 10.1126/science.2997930. [DOI] [PubMed] [Google Scholar]
  24. Shulman H. M., Hackman R. C., Sale G. E., Meyers J. D. Rapid cytologic diagnosis of cytomegalovirus interstitial pneumonia on touch imprints from open-lung biopsy. Am J Clin Pathol. 1982 Jan;77(1):90–94. doi: 10.1093/ajcp/77.1.90. [DOI] [PubMed] [Google Scholar]
  25. Smith T. F., Holley K. E., Keys T. F., Macasaet F. F. Cytomegalovirus studies of autopsy tissue. I. Virus isolation. Am J Clin Pathol. 1975 Jun;63(6):854–858. doi: 10.1093/ajcp/63.6.854. [DOI] [PubMed] [Google Scholar]
  26. Spector S. A. Transmission of cytomegalovirus among infants in hospital documented by restriction-endonuclease-digestion analyses. Lancet. 1983 Feb 19;1(8321):378–381. doi: 10.1016/s0140-6736(83)91499-x. [DOI] [PubMed] [Google Scholar]
  27. Stagno S., Pass R. F., Dworsky M. E., Henderson R. E., Moore E. G., Walton P. D., Alford C. A. Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection. N Engl J Med. 1982 Apr 22;306(16):945–949. doi: 10.1056/NEJM198204223061601. [DOI] [PubMed] [Google Scholar]
  28. Tabibzadeh S. S., Gerber M. A., Satyaswaroop P. G. Induction of HLA-DR antigen expression in human endometrial epithelial cells in vitro by recombinant gamma-interferon. Am J Pathol. 1986 Oct;125(1):90–96. [PMC free article] [PubMed] [Google Scholar]
  29. Unger E. R., Budgeon L. R., Myerson D., Brigati D. J. Viral diagnosis by in situ hybridization. Description of a rapid simplified colorimetric method. Am J Surg Pathol. 1986 Jan;10(1):1–8. doi: 10.1097/00000478-198601000-00001. [DOI] [PubMed] [Google Scholar]
  30. Vallejos H., Del Mistro A., Kleinhaus S., Braunstein J. D., Halwer M., Koss L. G. Characterization of human papilloma virus types in condylomata acuminata in children by in situ hybridization. Lab Invest. 1987 Jun;56(6):611–615. [PubMed] [Google Scholar]
  31. Volpi A., Whitley R. J., Ceballos R., Stagno S., Pereira L. Rapid diagnosis of pneumonia due to cytomegalovirus with specific monoclonal antibodies. J Infect Dis. 1983 Jun;147(6):1119–1120. doi: 10.1093/infdis/147.6.1119. [DOI] [PubMed] [Google Scholar]
  32. Wang N. S., Huang S. N., Thurlbeck W. M. Combined Pneumocystis carinii and cytomegalovirus infection. Arch Pathol. 1970 Dec;90(6):529–535. [PubMed] [Google Scholar]
  33. Wiley C. A., Schrier R. D., Denaro F. J., Nelson J. A., Lampert P. W., Oldstone M. B. Localization of cytomegalovirus proteins and genome during fulminant central nervous system infection in an AIDS patient. J Neuropathol Exp Neurol. 1986 Mar;45(2):127–139. doi: 10.1097/00005072-198603000-00003. [DOI] [PubMed] [Google Scholar]
  34. Winston D. J., Ho W. G., Howell C. L., Miller M. J., Mickey R., Martin W. J., Lin C. H., Gale R. P. Cytomegalovirus infections associated with leukocyte transfusions. Ann Intern Med. 1980 Nov;93(5):671–675. doi: 10.7326/0003-4819-93-5-671. [DOI] [PubMed] [Google Scholar]
  35. Winston D. J., Ho W. G., Young L. S., Gale R. P. Prophylactic granulocyte transfusions during human bone marrow transplantation. Am J Med. 1980 Jun;68(6):893–897. doi: 10.1016/0002-9343(80)90223-5. [DOI] [PubMed] [Google Scholar]

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