Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies.

Seefried M, Hundhausen N, Kroeger I, Büttner-Herold M, Hoffmann P, Edinger M, Ullrich E, Berberich-Siebelt F, Britt WJ, Mach M, Winkler T (2023)

Publication Type: Journal article

Publication year: 2023

Journal

JCI Insight American Society for Clinical Investigation

Book Volume: 8

Journal Issue: 5

DOI: 10.1172/jci.insight.149648

Abstract

Reactivation of human cytomegalovirus (HCMV) from latency is a frequent complication following hematopoietic stem cell transplantation (HSCT). The development of acute graft-versus-host disease (GVHD) is a significant risk factor for HCMV disease. Using a murine GVHD model in animals latently infected with murine CMV (MCMV), we studied preventive and therapeutic interventions in this high-risk scenario of HSCT. Mice latently infected with MCMV experienced reactivated MCMV and developed disseminated MCMV infection concomitant with the manifestations of GVHD. Dissemination was accompanied by accelerated mortality. We demonstrate that MCMV reactivation and dissemination was modulated by MCMV-specific antibodies, thus demonstrating in vivo protective activity of antiviral antibodies. However, the efficacy of serum therapy required repetitive doses of high-titer immune serum secondary to the shortened serum half-life of IgG in animals with GVHD. In a complementary approach, treatment of GVHD by adoptive transfer of donor-derived Tregs facilitated production of MCMV-specific antibodies from newly developing donor-derived B cells. Together, our findings strongly suggest that antibodies play a major role in controlling recurrent MCMV infection that follows GVHD, and they argue for reassessing the potential of antibody treatments as well as therapeutic strategies that enhance de novo antibody development against HCMV.

Authors with CRIS profile

Martina Seefried
Maike Büttner-Herold Department of Nephropathology Thomas Winkler Professur für Genetik

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung FAU Profilzentrum Licht.Materie.Quantentechnologien (FAU LMQ)

Related research project(s)

A096: Molecular and functional analysis of immune/ intestinal epithelial cell-interaction during CMV infection Jan. 1, 2023 - June 30, 2025

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) University of Alabama at Birmingham (UAB) US United States (USA) (US)

How to cite

APA:

Seefried, M., Hundhausen, N., Kroeger, I., Büttner-Herold, M., Hoffmann, P., Edinger, M.,... Winkler, T. (2023). Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies. JCI Insight, 8(5). https://doi.org/10.1172/jci.insight.149648

MLA:

Seefried, Martina, et al. "Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies." JCI Insight 8.5 (2023).

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