{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:05:33Z","timestamp":1790129133480,"version":"4.0.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n            <jats:title>Background.<\/jats:title>\n            <jats:p>Cytomegalovirus (CMV) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. Here, we describe the development and use of an assay to monitor the incidence and treatment of CMV viremia in a Cynomolgus macaque model of bone marrow transplantation (BMT) for tolerance induction. We address the correlation between the course of viremia and immune reconstitution.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods.<\/jats:title>\n            <jats:p>Twenty-one animals received a nonmyeloablative conditioning regimen. Seven received cyclosporine A for 28 days and 14 received rapamycin. A CMV polymerase chain reaction assay was developed and run twice per week to monitor viremia. Nineteen recipients were CMV seropositive before BMT. Immune reconstitution was monitored through flow cytometry and CMV viremia was tracked via quantitative polymerase chain reaction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results.<\/jats:title>\n            <jats:p>Recipients developed CMV viremia during the first month post-BMT. Two animals developed uncontrollable CMV disease. CMV reactivation occurred earlier in cyclosporine A-treated animals compared with those receiving rapamycin. Post-BMT, T-cell counts remained significantly lower compared with pretransplant levels until CMV reactivation, at which point they increased during the viremic phase and approached pretransplant levels 3 months post-BMT. Management of CMV required treatment before viremia reached 10 000 copies\/mL; otherwise clinical symptoms were observed. High doses of ganciclovir resolved the viremia, which could subsequently be controlled with valganciclovir.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions.<\/jats:title>\n            <jats:p>We developed an assay to monitor CMV in Cynomolgus macaques. CMV reactivation occurred in 100% of seropositive animals in this model. Rapamycin delayed CMV reactivation and ganciclovir treatment was effective at high doses. As in humans, CD8<jats:sup>+<\/jats:sup> T cells proliferated during CMV viremia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/tp.0000000000002893","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T16:41:37Z","timestamp":1565023297000},"page":"270-279","source":"Crossref","is-referenced-by-count":4,"title":["Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques"],"prefix":"10.1097","volume":"104","author":[{"given":"Paula","family":"Alonso-Guallart","sequence":"first","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimon","family":"Duran-Struuck","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."},{"name":"Department of Pathobiology, University of Pennsylvania, Philadelphia, PA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah S.","family":"Zitsman","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Sameroff","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Pereira","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Stern","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Berglund","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaly","family":"Llore","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Pierre","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Lopes","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal B.","family":"Kofman","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makenzie","family":"Danton","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo P.","family":"Sondermeijer","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."},{"name":"Department of Physiology, Maastricht University, Maastricht, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Woodland","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yojiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilrukshi K.","family":"Ekanayake-Alper","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina C.","family":"Iuga","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Shie","family":"Wuu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Wu","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Ian","family":"Lipkin","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Tokarz","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Sykes","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."},{"name":"Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY."},{"name":"Department of Surgery, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Griesemer","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY."},{"name":"Department of Surgery, Columbia University Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20231002","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1086\/508173","article-title":"Seroprevalence of cytomegalovirus infection in the United States, 1988-1994.","volume":"43","author":"Staras","year":"2006","journal-title":"Clin Infect Dis"},{"key":"R2-20231002","doi-asserted-by":"crossref","first-page":"aaa0698","DOI":"10.1126\/science.aaa0698","article-title":"Viral immunology. 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T-cell subsets in the peripheral blood of renal transplant recipients with sirolimus versus cyclosporine: a preliminary study.","volume":"45","author":"Zhao","year":"2013","journal-title":"Transplant Proc"},{"key":"R21-20231002","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1111\/j.1600-6143.2010.03119.x","article-title":"Phenotype, distribution and alloreactive properties of memory T cells from cynomolgus monkeys.","volume":"10","author":"Nadazdin","year":"2010","journal-title":"Am J Transplant"},{"key":"R22-20231002","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1093\/clinids\/4.6.1119","article-title":"Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years\u2019 experience.","volume":"4","author":"Meyers","year":"1982","journal-title":"Rev Infect Dis"},{"key":"R23-20231002","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/infdis\/153.3.478","article-title":"Risk factors for cytomegalovirus infection after human marrow transplantation.","volume":"153","author":"Meyers","year":"1986","journal-title":"J Infect Dis"},{"key":"R24-20231002","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/cid\/ciu364","article-title":"Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.","volume":"59","author":"Ljungman","year":"2014","journal-title":"Clin Infect Dis"},{"key":"R25-20231002","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1182\/blood-2015-11-679639","article-title":"Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis.","volume":"127","author":"Teira","year":"2016","journal-title":"Blood"},{"key":"R26-20231002","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.virol.2010.12.049","article-title":"Isolation and characterization of cynomolgus macaque (Macaca fascicularis) 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transplantation.","volume":"121","author":"Blyth","year":"2013","journal-title":"Blood"},{"key":"R36-20231002","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJM199510193331603","article-title":"Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor.","volume":"333","author":"Walter","year":"1995","journal-title":"N Engl J Med"},{"key":"R37-20231002","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/ajt.13023","article-title":"Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient.","volume":"15","author":"Macesic","year":"2015","journal-title":"Am J Transplant"},{"key":"R38-20231002","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1038\/cti.2015.5","article-title":"Adoptive T-cell immunotherapy for ganciclovir-resistant CMV disease after lung 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