Inflammatory cells in transplanted kidneys are infected by human cytomegalovirus. (original) (raw)

• Journal List
• Am J Pathol
• v.132(2); 1988 Aug
• PMC1880719

Am J Pathol. 1988 Aug; 132(2): 239–248.

Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Abstract

To determine which cells in kidney grafts are infected with human cytomegalovirus (HCMV) before and after transplantation, kidney specimens were studied by in situ hybridization with 35S-labeled DNA probes representing HCMV immediate-early and late genes. Pretransplantation biopsies and serial posttransplantation biopsies were obtained from 7 renal grafts. All of the transplant recipients were HCMV-seronegative at the time of transplantation and all developed primary HCMV infections. HCMV nucleic acids were not detected in biopsies taken from the healthy donor kidneys before transplantation. However, biopsies taken at various intervals after transplantation showed abundant hybridization with HCMV immediate-early and late gene probes. Virtually all of the hybridizing cells were mononuclear inflammatory cells in the interstitial spaces of the kidney. Occasional hybridization was seen with renal tubular or glomerular cells. No cytomegalic cells were seen. Biopsy specimens taken after systemic anti-HCMV chemotherapy with phosphonoformate showed no uniform reduction in HCMV gene expression. These studies demonstrate that the principal HCMV-infected cells in kidneys of renal transplant patients with primary HCMV infections are infiltrating inflammatory cells.

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• Peterson PK, Balfour HH, Jr, Marker SC, Fryd DS, Howard RJ, Simmons RL. 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]
• Glenn J. Cytomegalovirus infections following renal transplantation. Rev Infect Dis. 1981 Nov-Dec;3(6):1151–1178. [PubMed] [Google Scholar]
• Marker SC, Howard RJ, Simmons RL, Kalis JM, Connelly DP, Najarian JS, Balfour HH., Jr Cytomegalovirus infection: a quantitative prospective study of three hundred twenty consecutive renal transplants. Surgery. 1981 Jun;89(6):660–671. [PubMed] [Google Scholar]
• Betts RF. Cytomegalovirus infection in transplant patients. Prog Med Virol. 1982;28:44–64. [PubMed] [Google Scholar]
• Peterson PK, Ferguson R, Fryd DS, Balfour HH, Jr, Rynasiewicz J, Simmons RL. Infectious diseases in hospitalized renal transplant recipients: a prospective study of a complex and evolving problem. Medicine (Baltimore) 1982 Nov;61(6):360–372. [PubMed] [Google Scholar]
• Betts RF, Freeman RB, Douglas RG, Jr, Talley TE. Clinical manifestations of renal allograft derived primary cytomegalovirus infection. Am J Dis Child. 1977 Jul;131(7):759–763. [PubMed] [Google Scholar]
• Rubin RH, Cosimi AB, Tolkoff-Rubin NE, Russell PS, Hirsch MS. Infectious disease syndromes attributable to cytomegalovirus and their significance among renal transplant recipients. Transplantation. 1977 Dec;24(6):458–464. [PubMed] [Google Scholar]
• Suwansirikul S, Rao N, Dowling JN, Ho M. Primary and secondary cytomegalovirus infection. Arch Intern Med. 1977 Aug;137(8):1026–1029. [PubMed] [Google Scholar]
• Olding LB, Jensen FC, Oldstone MB. Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. J Exp Med. 1975 Mar 1;141(3):561–572. [PMC free article] [PubMed] [Google Scholar]
• Hamilton JD, Seaworth BJ. Transmission of latent cytomegalovirus in a murine kidney tissue transplantation model. Transplantation. 1985 Mar;39(3):290–296. [PubMed] [Google Scholar]
• Klotman ME, Starnes D, Hamilton JD. The source of murine cytomegalovirus in mice receiving kidney allografts. J Infect Dis. 1985 Dec;152(6):1192–1196. [PubMed] [Google Scholar]
• Bruning JH, Bruggeman CA, van Boven CP, van Breda Vriesman PJ. Passive transfer of cytomegalovirus by cardiac and renal organ transplants in a rat model. Transplantation. 1986 Jun;41(6):695–698. [PubMed] [Google Scholar]
• Porter KR, Starnes DM, Hamilton JD. Reactivation of latent murine cytomegalovirus from kidney. Kidney Int. 1985 Dec;28(6):922–925. [PubMed] [Google Scholar]
• Ho M, Suwansirikul S, Dowling JN, Youngblood LA, Armstrong JA. The transplanted kidney as a source of cytomegalovirus infection. N Engl J Med. 1975 Nov 27;293(22):1109–1112. [PubMed] [Google Scholar]
• Smiley ML, Wlodaver CG, Grossman RA, Barker CF, Perloff LJ, Tustin NB, Starr SE, Plotkin SA, Friedman HM. The role of pretransplant immunity in protection from cytomegalovirus disease following renal transplantation. Transplantation. 1985 Aug;40(2):157–161. [PubMed] [Google Scholar]
• Nankervis GA. Comments on CMV infections in renal transplant patients. Yale J Biol Med. 1976 Mar;49(1):27–28. [PMC free article] [PubMed] [Google Scholar]
• Balfour HH, Jr, Slade MS, Kalis JM, Howard RJ, Simmons RL, Najarian JS. Viral infections in renal transplant donors and their recipients: a prospective study. Surgery. 1977 May;81(5):487–492. [PubMed] [Google Scholar]
• Naraqi S, Jackson GG, Jonasson O, Rubenis M. Search for latent cytomegalovirus in renal allografts. Infect Immun. 1978 Feb;19(2):699–703. [PMC free article] [PubMed] [Google Scholar]
• Orsi EV, Howard JL, Baturay N, Ende N, Ribot S, Eslami H. High incidence of virus isolation from donor and recipient tissues associated with renal transplantation. Nature. 1978 Mar 23;272(5651):372–373. [PubMed] [Google Scholar]
• Herrera GA, Alexander RW, Cooley CF, Luke RG, Kelly DR, Curtis JJ, Gockerman JP. Cytomegalovirus glomerulopathy: a controversial lesion. Kidney Int. 1986 Mar;29(3):725–733. [PubMed] [Google Scholar]
• Lang DJ, Ebert PA, Rodgers BM, Boggess HP, Rixse RS. Reduction of postperfusion cytomegalovirus-infections following the use of leukocyte depleted blood. Transfusion. 1977 Jul-Aug;17(4):391–395. [PubMed] [Google Scholar]
• Schrier RD, Nelson JA, Oldstone MB. Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science. 1985 Nov 29;230(4729):1048–1051. [PubMed] [Google Scholar]
• Wiley CA, Schrier RD, Denaro FJ, Nelson JA, Lampert PW, Oldstone MB. 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. [PubMed] [Google Scholar]
• Demarchi JM. Human cytomegalovirus DNA: restriction enzyme cleavage maps and map locations for immediate-early, early, and late RNAs. Virology. 1981 Oct 15;114(1):23–38. [PubMed] [Google Scholar]
• Wathen MW, Stinski MF. Temporal patterns of human cytomegalovirus transcription: mapping the viral RNAs synthesized at immediate early, early, and late times after infection. J Virol. 1982 Feb;41(2):462–477. [PMC free article] [PubMed] [Google Scholar]
• Rice GP, Schrier RD, Oldstone MB. 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. [PMC free article] [PubMed] [Google Scholar]
• Jahn G, Knust E, Schmolla H, Sarre T, Nelson JA, McDougall JK, Fleckenstein B. Predominant immediate-early transcripts of human cytomegalovirus AD 169. J Virol. 1984 Feb;49(2):363–370. [PMC free article] [PubMed] [Google Scholar]
• Stenberg RM, Witte PR, Stinski MF. Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1. J Virol. 1985 Dec;56(3):665–675. [PMC free article] [PubMed] [Google Scholar]
• Rüger B, Klages S, Walla B, Albrecht J, Fleckenstein B, Tomlinson P, Barrell B. Primary structure and transcription of the genes coding for the two virion phosphoproteins pp65 and pp71 of human cytomegalovirus. J Virol. 1987 Feb;61(2):446–453. [PMC free article] [PubMed] [Google Scholar]
• Nowak B, Gmeiner A, Sarnow P, Levine AJ, Fleckenstein B. Physical mapping of human cytomegalovirus genes: identification of DNA sequences coding for a virion phosphoprotein of 71 kDa and a viral 65-kDa polypeptide. Virology. 1984 Apr 15;134(1):91–102. [PMC free article] [PubMed] [Google Scholar]
• Fleckenstein B, Müller I, Collins J. Cloning of the complete human cytomegalovirus genome in cosmids. Gene. 1982 Apr;18(1):39–46. [PubMed] [Google Scholar]
• Rigby PW, 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. [PubMed] [Google Scholar]
• Hancock WW, Thomson NM, Atkins RC. Composition of interstitial cellular infiltrate identified by monoclonal antibodies in renal biopsies of rejecting human renal allografts. Transplantation. 1983 May;35(5):458–463. [PubMed] [Google Scholar]
• Hall BM, Bishop GA, Farnsworth A, Duggin GG, Horvath JS, Sheil AG, Tiller DJ. Identification of the cellular subpopulations infiltrating rejecting cadaver renal allografts. Preponderance of the T4 subset of T cells. Transplantation. 1984 Jun;37(6):564–570. [PubMed] [Google Scholar]
• McWhinnie DL, Thompson JF, Taylor HM, Chapman JR, Bolton EM, Carter NP, Wood RF, Morris PJ. Morphometric analysis of cellular infiltration assessed by monoclonal antibody labeling in sequential human renal allograft biopsies. Transplantation. 1986 Oct;42(4):352–358. [PubMed] [Google Scholar]
• Fetterman GH, Sherman FE, Fabrizio NS, Studnicki FM. Generalized cytomegalic inclusion disease of the newborn. Localization of inclusions in the kidney. Arch Pathol. 1968 Jul;86(1):86–94. [PubMed] [Google Scholar]
• Heieren MH, van der Woude FJ, Balfour HH., Jr Cytomegalovirus replicates efficiently in human kidney mesangial cells. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1642–1646. [PMC free article] [PubMed] [Google Scholar]
• Braun RW, Reiser HC. Replication of human cytomegalovirus in human peripheral blood T cells. J Virol. 1986 Oct;60(1):29–36. [PMC free article] [PubMed] [Google Scholar]
• Wu BC, Dowling JN, Armstrong JA, Ho M. Enhancement of mouse cytomegalovirus infection during host-versus-graft reaction. Science. 1975 Oct 3;190(4209):56–58. [PubMed] [Google Scholar]
• Jordan MC, Shanley JD, Stevens JG. Immunosuppression reactivates and disseminates latent murine cytomegalovirus. J Gen Virol. 1977 Nov;37(2):419–423. [PubMed] [Google Scholar]
• Helgstrand E, Eriksson B, Johansson NG, Lannerö B, Larsson A, Misiorny A, Norén JO, Sjöberg B, Stenberg K, Stening G, et al. Trisodium phosphonoformate, a new antiviral compound. Science. 1978 Sep 1;201(4358):819–821. [PubMed] [Google Scholar]
• Ahlmén J, Wijnween AC, Brynger H, Lycke E. Clinical experiences with phosphonoformate (foscarnet) treatment of viral diseases following renal transplantation. Scand J Urol Nephrol Suppl. 1985;92:41–44. [PubMed] [Google Scholar]
• Lopez C, Simmons RL, Mauer SM, Najarian JS, Good RA, Gentry S. Association of renal allograft rejection with virus infections. Am J Med. 1974 Mar;56(3):280–289. [PubMed] [Google Scholar]
• Simmons RL, Lopez C, Balfour H, Jr, Kalis J, Rattazzi LC, Najarian JS. Cytomegalovirus: Clinical virological correlations in renal transplant recipients. Ann Surg. 1974 Oct;180(4):623–634. [PMC free article] [PubMed] [Google Scholar]
• Cappel R, Hestermans O, Toussaint C, Vereerstraeten P, van Beers D, de Braekeleer J, Schoutens E. Cytomegalovirus infection and graft survival in renal graft recipients. Arch Virol. 1978;56(1-2):149–156. [PubMed] [Google Scholar]
• May AG, Betts RF, Freeman RB, Andrus CH. An analysis of cytomegalovirus infection and HLA antigen matching on the outcome of renal transplantation. Ann Surg. 1978 Feb;187(2):110–117. [PMC free article] [PubMed] [Google Scholar]
• Pass RF, Whitley RJ, Diethelm AG, Whelchel JD, Reynolds DW, Alford CA., Jr Outcome of renal transplantation in patients with primary cytomegalovirus infection. Transplant Proc. 1979 Jun;11(2):1288–1290. [PubMed] [Google Scholar]
• van Es A, Baldwin WM, Oljans PJ, Tanke HJ, Ploem JS, van Es LA. Expression of HLA-DR on T lymphocytes following renal transplantation, and association with graft-rejection episodes and cytomegalovirus infection. Transplantation. 1984 Jan;37(1):65–69. [PubMed] [Google Scholar]
• Rubin RH, Tolkoff-Rubin NE, Oliver D, Rota TR, Hamilton J, Betts RF, Pass RF, Hillis W, Szmuness W, Farrell ML, et al. Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation. Transplantation. 1985 Sep;40(3):243–249. [PubMed] [Google Scholar]

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