Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies
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 infect...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-03-01
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| Series: | JCI Insight |
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| Online Access: | https://doi.org/10.1172/jci.insight.149648 |
| _version_ | 1827768033669545984 |
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| author | Martina Seefried Nadine Hundhausen Irena Kroeger Maike Büttner-Herold Petra Hoffmann Matthias Edinger Evelyn Ullrich Friederike Berberich-Siebelt William J. Britt Michael Mach Thomas H. Winkler |
| author_facet | Martina Seefried Nadine Hundhausen Irena Kroeger Maike Büttner-Herold Petra Hoffmann Matthias Edinger Evelyn Ullrich Friederike Berberich-Siebelt William J. Britt Michael Mach Thomas H. Winkler |
| author_sort | Martina Seefried |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T12:06:45Z |
| format | Article |
| id | doaj.art-85e5e8164bca4a6aa5ac4dbeda5eced2 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:06:45Z |
| publishDate | 2023-03-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-85e5e8164bca4a6aa5ac4dbeda5eced22023-11-07T16:25:19ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-03-0185Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodiesMartina SeefriedNadine HundhausenIrena KroegerMaike Büttner-HeroldPetra HoffmannMatthias EdingerEvelyn UllrichFriederike Berberich-SiebeltWilliam J. BrittMichael MachThomas H. WinklerReactivation 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.https://doi.org/10.1172/jci.insight.149648HematologyImmunology |
| spellingShingle | Martina Seefried Nadine Hundhausen Irena Kroeger Maike Büttner-Herold Petra Hoffmann Matthias Edinger Evelyn Ullrich Friederike Berberich-Siebelt William J. Britt Michael Mach Thomas H. Winkler Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies JCI Insight Hematology Immunology |
| title | Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies |
| title_full | Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies |
| title_fullStr | Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies |
| title_full_unstemmed | Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies |
| title_short | Murine cytomegalovirus reactivation concomitant with acute graft-versus-host disease is controlled by antibodies |
| title_sort | murine cytomegalovirus reactivation concomitant with acute graft versus host disease is controlled by antibodies |
| topic | Hematology Immunology |
| url | https://doi.org/10.1172/jci.insight.149648 |
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