Summary
Infection with cytomegalovirus is a major concern following bone marrow transplantation. Previously, we have described a model whereby infection by MCMV concurrent with the injection of parental strain lymphoid cells into F1 recipient mice results in a severe graft-versus-host reaction (GvHR) when the donor and host differ at the class I MHC locus (i.e., class I MHC disparate GvHR). The present studies were performed to determine whether one consequence of this severe GvHR is the alteration of the tissue distribution and/or levels of infectious virus as compared to mice not undergoing GvHR. Using PCR to detect MCMV DNA, it was observed that the tissue distribution of virus 3 days after injection was identical in recipients of virus alone and of GvHR plus virus inocula. At two weeks post injection, virus was recovered from the salivary gland and pancreas in both groups. In contrast to recipients of MCMV alone, lung tissue from GvHR plus virus mice also contained viral DNA. Notably, these results were corroborated by the plaque assay. Moreover, salivary gland and pancreas from recipients of GvHR plus virus were found to contain higher titers of infectious virus. In total, the data demonstrate that, with the notable exception of the lung, the distribution of virus was not changed in the animals despite the presence of a concurrent severe GvHR. However, viral replication in infected tissues appeared less restricted in these recipients.
Similar content being viewed by others
References
Bostrom L, Ringden O, Sundberg B, Linde A, Tollemar J, Nilsson B (1988) Pretransplant herpesvirus serology and acute graft-versus-host disease. Transplantation 46: 548–552
Gratama JW, Stijnen T, Weiland HT, Hekker AC, de Gast GC, Zwaan FE, Weijers TF, D'Amaro J, The TH, Vossen JMJJ (1987) Herpes-virus immunity and acute graft-versus-host disease. Lancet i: 471–474
Lonnqvist B, Ringden O, Wahren B, Gahrton G, Lundgren G (1984) Cytomegalovirus infection associated with and preceding chronic graft-versus-host disease. Transplantation 38: 465–468
Meyers JD, Shepp DH, Bowden RA, Reed EC (1989) Viral infections in marrow transplant recipients. In: Gale RP, Champlin RE (eds) Progress in bone marrow transplantation. AR Liss, New York, pp 545–562
Ringden O, Bostrom L, Paulin T (1989) On herpes virus immunity, graft-versus-host disease, pneumonitis and relapse. In: Gale RP, Champlin RE (eds) Progress in bone marrow transplantation. AR Liss, New York, pp 573–598
Winston DJ, Gale RP, Meyer DV, Young LS (1979) Infectious complications of human bone marrow transplantation. Medicine 58: 1–30
Grundy JE, Shanley JD, Shearer GM (1985) Augmentation of graft-versus-host reaction by cytomegalovirus infection resulting in interstitial pneumonitis. Transplantation 39: 548–553
Cray C, Levy RB (1989) The ability of murine cytomegalovirus and class I major histocompatability complex-disparate parental cells to induce alterations characteristic of severe graft-versus-host reactions. Transplantation 48: 1057–1063
Levy RB, Jones M, Cray C (1990) HSV-1 enhances graft-versus-host reaction associated parent anti-F1 alloreactivity in vivo and in vitro. Cell Immunol 129: 1–12
Saiki RK, Scharf S, Faloona F (1985) Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230: 1350–1350
Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor
Crouse CA, Pauley RJ (1989) Molecular cloning and sequencing of the Mtv-1 LTR: Evidence for a LTR sequence alteration. Virus Res 12: 123–137
Keil GM, Ebeling-Keil A, Koszinowski UH (1987) Sequence and structural organization of murine cytomegalovirus immediate-early gene 1. J Virol 61: 1901–1908
Meyers JD, Flournoy N, Thomas ED (1980) Cytomegalovirus infection and specific cell-mediated immunity after marrow transplant. J Infect Dis 142: 816–824
Meyers JD, Flournoy N, Thomas ED (1986) Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis 153: 478–488
Cray C, Levy RB (1990) Virus-associated immune responses in mice undergoing GvHR exacerbated by concurrent MCMV infection. Transplantation 50: 1027–1032
Cray C, Levy RB (1990) The presence of infectious virus but not conventional antigen can exacerbate graft-versus-host reactions. Scand J Immunol 32: 177–182
Grundy JE, Shanley JD, Griffiths PD (1987) Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition? Lancet ii: 996–999
Shanley JD, Via CS, Sharrow SO, Shearer GM (1987) Interstitial pneumonitis during murine cytomegalovirus infection and graft-versus-host reaction. Transplantation 44: 658–662
Allan JE, Shellam GR (1984) Genetic control of murine cytomegalovirus infection: virus titres in resistant and susceptible strains of mice. Arch Virol 81: 139–150
Chalmer JE, Mackenzie JS, Stanley NF (1977) Resistance to murine cytomegalovirus linked to the major histocompatibility complex of the mouse. J Gen Virol 37: 107–114
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cray, C., Crouse, C., Atherton, S.S. et al. Effect of concurrent graft-versus-host reaction on tissue distribution and infectious titer of murine cytomegalovirus. Archives of Virology 121, 101–110 (1991). https://doi.org/10.1007/BF01316747
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01316747