The Source of Murine Cytomegalovirus in Mice Receiving Kidney Allografts

Klotman, Mary E.; Starnes, Diane M.; Hamilton, John D.

doi:10.1093/infdis/152.6.1192

Cited by 20 publications

(12 citation statements)

References 12 publications

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“…18,19 However, later, a dominant MCMV resistance trait expressed by C57BL/6 mice used as recipients in these studies was suggested, which therefore limited the scope of these results. Experimental models have suggested that a large proportion of mouse CMV (MCMV) viremia in D+R+ recipients originated from the recipient.…”

Section: Discussionmentioning

confidence: 99%

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells

Al-Hajj

Noble

Chevallier

et al. 2018

American Journal of Transplantation

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We aimed to determine the role of cytomegalovirus (CMV)-infected donor cells in the development of a CMV-specific immune response in kidney transplant recipients. We assessed the CMV pp65-specific immune response by using interferon-ɣ ELISPOT and dextramers in peripheral blood mononuclear cells from 115 recipients (D+R- 31, D+R + 44, D-R + 40) late after transplantation (mean 59 ± 42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN-ɣ-producing anti-CMV T cells (P = .004). This effect disappeared with the absence of shared HLA class I specificities between donors and recipients (P = .430). To confirm the role of donor cells in stimulating the expansion of newly developed CMV-specific CD8 T cells after transplantation, we compared the number of HLA-A2-restricted CMV-specific CD8 T cells in primo-infected recipients who received an HLA-A2 or non-HLA-A2 graft. The median of anti-CMV pp65 T cells restricted by HLA-A2 was very low for patients who received a non-HLA-A2 graft vs an HLA-A2 graft (300 [0-14638] vs. 17972 [222-85594] anti-CMV pp65 CD8 T cells/million CD8 T cells, P = .001). This adds new evidence that CMV-infected kidney donor cells present CMV peptides and drive an inflation of memory CMV-specific CD8 T cells, likely because of frequent CMV replications within the graft.

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Section: Discussionmentioning

confidence: 99%

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells

Al-Hajj

Noble

Chevallier

et al. 2018

American Journal of Transplantation

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“…These findings strongly argued against T and B lymphocytes, macrophages, and dendritic cells (DCs) being major reservoirs of latent mCMV in the spleen, a conclusion supported by later work of Pomeroy and colleagues (86). Sim-ilarly, Klotman and colleagues (54) as well as Hamilton and Seaworth (44) concluded that in kidney transplantation, donor kidney is the source of latent mCMV and that the latent viral genome is harbored by renal peritubular epithelial cells (53). A first hint for mCMV latency in ECs within the liver was provided by in situ PCR images presented by Koffron and colleagues (59) showing nuclear staining in cells with a microanatomical localization suspicious of liver sinusoidal ECs (LSECs).…”

mentioning

confidence: 99%

Liver Sinusoidal Endothelial Cells Are a Site of Murine Cytomegalovirus Latency and Reactivation

Seckert

Renzaho

Tervo

et al. 2009

J Virol

105

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In human cytomegalovirus (hCMV) infection, hematopoietic progenitor cells of the myeloid differentiation lineage are a recognized cellular site of virus latency (for more-recent reviews, see references 75 and 94), and cell differentiationdependent as well as cytokine-mediated viral gene desilencing by chromatin remodeling is discussed as the triggering event leading to virus reactivation (for a review, see reference 7). Although hematopoietic stem cell or bone marrow transplantation (BMT) is frequently associated with hCMV reactivation and recurrence in recipients after hematoablative leukemia/ lymphoma therapy, the incidence of virus recurrence and disease is highest in the combination of an hCMV-negative donor (D

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“…Latent infection has been demonstrated in the spleen (15,28,38,39), kidney (14,18), salivary gland (6,48), and lung (3). In addition, human hematopoietic cells, including bone marrow cells, have been found to contain latent HCMV (12,30).…”

mentioning

confidence: 99%

Reactivation of Latent Cytomegalovirus Infection in Mouse Brain Cells Detected after Transfer to Brain Slice Cultures

Tsutsui

Kawasaki

Kosugi

2002

J Virol

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Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders in humans involving the developing brain. It is hypothesized that the brain disorders occur after recurrent reactivation of the latent infection in some kinds of cells in the brains. In order to test this hypothesis, we examined the reactivation of latent murine CMV (MCMV) infection in the mouse brain by transfer to brain slice culture. We infected neonatal and young adult mice intracerebrally with recombinant MCMV in which the lacZ gene was inserted into a late gene. The brains were removed 6 months after infection and used to prepare brain slices that were then cultured for up to 4 weeks. Reactivation of latent infection in the brains was detected by ␤-galactosidase (␤-Gal) staining to assess ␤-galactosidase expression. Viral replication was also confirmed by the plaque assay. Reactivation was observed in about 75% of the mice infected during the neonatal period 6 months after infection. Unexpectedly, reactivation was also observed in 75% of mice infected as young adults, although the infection ratio in the brain slices was significantly lower than that in neonatally infected mice. ␤-Gal-positive cells were observed in marginal regions of the brains or immature neural cells in the ventricular walls. Immunohistochemical staining showed that the ␤-Gal-positive reactivated cells were neural stem or progenitor cells. These results suggest that brain disorders may occur long after infection by reactivation of latent infection in the immature neural cells in the brain.

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The Source of Murine Cytomegalovirus in Mice Receiving Kidney Allografts

Cited by 20 publications

References 12 publications

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells

CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T cells restricted by shared class I HLA molecules via presentation on donor cells

Liver Sinusoidal Endothelial Cells Are a Site of Murine Cytomegalovirus Latency and Reactivation

Reactivation of Latent Cytomegalovirus Infection in Mouse Brain Cells Detected after Transfer to Brain Slice Cultures

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