RapamycinFungusV1, Main, Exploration, bibRecord, 000109

Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.

Identifieur interne : 000109 ( Main/Exploration ); précédent : 000108; suivant : 000110

Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.

Auteurs : Paula Alonso-Guallart [États-Unis] ; Raimon Duran-Struuck [États-Unis] ; Jonah S. Zitsman [États-Unis] ; Stephen Sameroff [États-Unis] ; Marcus Pereira [États-Unis] ; Jeffrey Stern [États-Unis] ; Erik Berglund [États-Unis] ; Nathaly Llore [États-Unis] ; Genevieve Pierre [États-Unis] ; Emily Lopes [États-Unis] ; Sigal B. Kofman [États-Unis] ; Makenzie Danton [États-Unis] ; Hugo P. Sondermeijer [États-Unis, Pays-Bas] ; David Woodland [États-Unis] ; Yojiro Kato [États-Unis] ; Dilrukshi K. Ekanayake-Alper [États-Unis] ; Alina C. Iuga [États-Unis] ; Cheng-Shie Wuu [États-Unis] ; Anette Wu [États-Unis] ; W Ian Lipkin [États-Unis] ; Rafal Tokarz [États-Unis] ; Megan Sykes [États-Unis] ; Adam Griesemer [États-Unis]

Source :

Transplantation [ 1534-6080 ] ; 2020.

RBID : pubmed:31385931

Descripteurs français

KwdFr :
- Activation virale (MeSH), Animaux (MeSH), Antifongiques (pharmacologie), Cytomegalovirus (immunologie), Infections à cytomégalovirus (immunologie), Infections à cytomégalovirus (thérapie), Infections à cytomégalovirus (virologie), Macaca fascicularis (MeSH), Modèles animaux de maladie humaine (MeSH), Receveurs de transplantation (MeSH), Reconstitution immunitaire (physiologie), Rejet du greffon (immunologie), Rejet du greffon (prévention et contrôle), Sirolimus (pharmacologie), Tolérance immunitaire (MeSH), Transplantation de moelle osseuse (méthodes).
MESH :
- immunologie : Cytomegalovirus, Infections à cytomégalovirus, Rejet du greffon.
- méthodes : Transplantation de moelle osseuse.
- pharmacologie : Antifongiques, Sirolimus.
- physiologie : Reconstitution immunitaire.
- prévention et contrôle : Rejet du greffon.
- thérapie : Infections à cytomégalovirus.
- virologie : Infections à cytomégalovirus.
- Activation virale, Animaux, Macaca fascicularis, Modèles animaux de maladie humaine, Receveurs de transplantation, Tolérance immunitaire.

English descriptors

KwdEn :
- Animals (MeSH), Antifungal Agents (pharmacology), Bone Marrow Transplantation (methods), Cytomegalovirus (immunology), Cytomegalovirus Infections (immunology), Cytomegalovirus Infections (therapy), Cytomegalovirus Infections (virology), Disease Models, Animal (MeSH), Graft Rejection (immunology), Graft Rejection (prevention & control), Immune Reconstitution (physiology), Immune Tolerance (MeSH), Macaca fascicularis (MeSH), Sirolimus (pharmacology), Transplant Recipients (MeSH), Virus Activation (MeSH).
MESH :
- chemical , pharmacology : Antifungal Agents, Sirolimus.
- immunology : Cytomegalovirus, Cytomegalovirus Infections, Graft Rejection.
- methods : Bone Marrow Transplantation.
- physiology : Immune Reconstitution.
- prevention & control : Graft Rejection.
- therapy : Cytomegalovirus Infections.
- virology : Cytomegalovirus Infections.
- Animals, Disease Models, Animal, Immune Tolerance, Macaca fascicularis, Transplant Recipients, Virus Activation.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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 T cells proliferated during CMV viremia.

DOI: 10.1097/TP.0000000000002893
PubMed: 31385931
PubMed Central: PMC6994365

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000215
to stream Main, to step Curation: 000215

Le document en format XML

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<wicri:cityArea>Department of Pathobiology, University of Pennsylvania, Philadelphia</wicri:cityArea>
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<author><name sortKey="Llore, Nathaly" sort="Llore, Nathaly" uniqKey="Llore N" first="Nathaly" last="Llore">Nathaly Llore</name>
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<author><name sortKey="Lopes, Emily" sort="Lopes, Emily" uniqKey="Lopes E" first="Emily" last="Lopes">Emily Lopes</name>
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<author><name sortKey="Kofman, Sigal B" sort="Kofman, Sigal B" uniqKey="Kofman S" first="Sigal B" last="Kofman">Sigal B. Kofman</name>
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<author><name sortKey="Danton, Makenzie" sort="Danton, Makenzie" uniqKey="Danton M" first="Makenzie" last="Danton">Makenzie Danton</name>
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<author><name sortKey="Sondermeijer, Hugo P" sort="Sondermeijer, Hugo P" uniqKey="Sondermeijer H" first="Hugo P" last="Sondermeijer">Hugo P. Sondermeijer</name>
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</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
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<affiliation wicri:level="1"><nlm:affiliation>Department of Physiology, Maastricht University, Maastricht, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
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<author><name sortKey="Woodland, David" sort="Woodland, David" uniqKey="Woodland D" first="David" last="Woodland">David Woodland</name>
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<author><name sortKey="Kato, Yojiro" sort="Kato, Yojiro" uniqKey="Kato Y" first="Yojiro" last="Kato">Yojiro Kato</name>
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<author><name sortKey="Ekanayake Alper, Dilrukshi K" sort="Ekanayake Alper, Dilrukshi K" uniqKey="Ekanayake Alper D" first="Dilrukshi K" last="Ekanayake-Alper">Dilrukshi K. Ekanayake-Alper</name>
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<country xml:lang="fr">États-Unis</country>
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</placeName>
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<author><name sortKey="Iuga, Alina C" sort="Iuga, Alina C" uniqKey="Iuga A" first="Alina C" last="Iuga">Alina C. Iuga</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pathology and Cell Biology, Columbia University, New York</wicri:cityArea>
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<author><name sortKey="Wuu, Cheng Shie" sort="Wuu, Cheng Shie" uniqKey="Wuu C" first="Cheng-Shie" last="Wuu">Cheng-Shie Wuu</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Radiation Oncology, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Radiation Oncology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
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<author><name sortKey="Wu, Anette" sort="Wu, Anette" uniqKey="Wu A" first="Anette" last="Wu">Anette Wu</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
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</affiliation>
</author>
<author><name sortKey="Lipkin, W Ian" sort="Lipkin, W Ian" uniqKey="Lipkin W" first="W Ian" last="Lipkin">W Ian Lipkin</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Tokarz, Rafal" sort="Tokarz, Rafal" uniqKey="Tokarz R" first="Rafal" last="Tokarz">Rafal Tokarz</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sykes, Megan" sort="Sykes, Megan" uniqKey="Sykes M" first="Megan" last="Sykes">Megan Sykes</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Surgery, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Griesemer, Adam" sort="Griesemer, Adam" uniqKey="Griesemer A" first="Adam" last="Griesemer">Adam Griesemer</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Surgery, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.</title>
<author><name sortKey="Alonso Guallart, Paula" sort="Alonso Guallart, Paula" uniqKey="Alonso Guallart P" first="Paula" last="Alonso-Guallart">Paula Alonso-Guallart</name>
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<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
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</author>
<author><name sortKey="Duran Struuck, Raimon" sort="Duran Struuck, Raimon" uniqKey="Duran Struuck R" first="Raimon" last="Duran-Struuck">Raimon Duran-Struuck</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathobiology, University of Pennsylvania, Philadelphia, PA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Pathobiology, University of Pennsylvania, Philadelphia</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zitsman, Jonah S" sort="Zitsman, Jonah S" uniqKey="Zitsman J" first="Jonah S" last="Zitsman">Jonah S. Zitsman</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sameroff, Stephen" sort="Sameroff, Stephen" uniqKey="Sameroff S" first="Stephen" last="Sameroff">Stephen Sameroff</name>
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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Pereira, Marcus" sort="Pereira, Marcus" uniqKey="Pereira M" first="Marcus" last="Pereira">Marcus Pereira</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Stern, Jeffrey" sort="Stern, Jeffrey" uniqKey="Stern J" first="Jeffrey" last="Stern">Jeffrey Stern</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Berglund, Erik" sort="Berglund, Erik" uniqKey="Berglund E" first="Erik" last="Berglund">Erik Berglund</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Llore, Nathaly" sort="Llore, Nathaly" uniqKey="Llore N" first="Nathaly" last="Llore">Nathaly Llore</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Pierre, Genevieve" sort="Pierre, Genevieve" uniqKey="Pierre G" first="Genevieve" last="Pierre">Genevieve Pierre</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lopes, Emily" sort="Lopes, Emily" uniqKey="Lopes E" first="Emily" last="Lopes">Emily Lopes</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kofman, Sigal B" sort="Kofman, Sigal B" uniqKey="Kofman S" first="Sigal B" last="Kofman">Sigal B. Kofman</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Danton, Makenzie" sort="Danton, Makenzie" uniqKey="Danton M" first="Makenzie" last="Danton">Makenzie Danton</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sondermeijer, Hugo P" sort="Sondermeijer, Hugo P" uniqKey="Sondermeijer H" first="Hugo P" last="Sondermeijer">Hugo P. Sondermeijer</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="1"><nlm:affiliation>Department of Physiology, Maastricht University, Maastricht, Netherlands.</nlm:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Physiology, Maastricht University, Maastricht</wicri:regionArea>
<wicri:noRegion>Maastricht</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Woodland, David" sort="Woodland, David" uniqKey="Woodland D" first="David" last="Woodland">David Woodland</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kato, Yojiro" sort="Kato, Yojiro" uniqKey="Kato Y" first="Yojiro" last="Kato">Yojiro Kato</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ekanayake Alper, Dilrukshi K" sort="Ekanayake Alper, Dilrukshi K" uniqKey="Ekanayake Alper D" first="Dilrukshi K" last="Ekanayake-Alper">Dilrukshi K. Ekanayake-Alper</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Iuga, Alina C" sort="Iuga, Alina C" uniqKey="Iuga A" first="Alina C" last="Iuga">Alina C. Iuga</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Pathology and Cell Biology, Columbia University, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Pathology and Cell Biology, Columbia University, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wuu, Cheng Shie" sort="Wuu, Cheng Shie" uniqKey="Wuu C" first="Cheng-Shie" last="Wuu">Cheng-Shie Wuu</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Radiation Oncology, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Radiation Oncology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wu, Anette" sort="Wu, Anette" uniqKey="Wu A" first="Anette" last="Wu">Anette Wu</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lipkin, W Ian" sort="Lipkin, W Ian" uniqKey="Lipkin W" first="W Ian" last="Lipkin">W Ian Lipkin</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Tokarz, Rafal" sort="Tokarz, Rafal" uniqKey="Tokarz R" first="Rafal" last="Tokarz">Rafal Tokarz</name>
<affiliation wicri:level="2"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Sykes, Megan" sort="Sykes, Megan" uniqKey="Sykes M" first="Megan" last="Sykes">Megan Sykes</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Microbiology and Immunology, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Surgery, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Griesemer, Adam" sort="Griesemer, Adam" uniqKey="Griesemer A" first="Adam" last="Griesemer">Adam Griesemer</name>
<affiliation wicri:level="2"><nlm:affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Department of Surgery, Columbia University Medical Center, New York, NY.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
<wicri:cityArea>Department of Surgery, Columbia University Medical Center, New York</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Transplantation</title>
<idno type="eISSN">1534-6080</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Antifungal Agents (pharmacology)</term>
<term>Bone Marrow Transplantation (methods)</term>
<term>Cytomegalovirus (immunology)</term>
<term>Cytomegalovirus Infections (immunology)</term>
<term>Cytomegalovirus Infections (therapy)</term>
<term>Cytomegalovirus Infections (virology)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Graft Rejection (immunology)</term>
<term>Graft Rejection (prevention & control)</term>
<term>Immune Reconstitution (physiology)</term>
<term>Immune Tolerance (MeSH)</term>
<term>Macaca fascicularis (MeSH)</term>
<term>Sirolimus (pharmacology)</term>
<term>Transplant Recipients (MeSH)</term>
<term>Virus Activation (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation virale (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Antifongiques (pharmacologie)</term>
<term>Cytomegalovirus (immunologie)</term>
<term>Infections à cytomégalovirus (immunologie)</term>
<term>Infections à cytomégalovirus (thérapie)</term>
<term>Infections à cytomégalovirus (virologie)</term>
<term>Macaca fascicularis (MeSH)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Receveurs de transplantation (MeSH)</term>
<term>Reconstitution immunitaire (physiologie)</term>
<term>Rejet du greffon (immunologie)</term>
<term>Rejet du greffon (prévention et contrôle)</term>
<term>Sirolimus (pharmacologie)</term>
<term>Tolérance immunitaire (MeSH)</term>
<term>Transplantation de moelle osseuse (méthodes)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antifungal Agents</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cytomegalovirus</term>
<term>Infections à cytomégalovirus</term>
<term>Rejet du greffon</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cytomegalovirus</term>
<term>Cytomegalovirus Infections</term>
<term>Graft Rejection</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Bone Marrow Transplantation</term>
</keywords>
<keywords scheme="MESH" qualifier="méthodes" xml:lang="fr"><term>Transplantation de moelle osseuse</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antifongiques</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Reconstitution immunitaire</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Immune Reconstitution</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Graft Rejection</term>
</keywords>
<keywords scheme="MESH" qualifier="prévention et contrôle" xml:lang="fr"><term>Rejet du greffon</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Cytomegalovirus Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="thérapie" xml:lang="fr"><term>Infections à cytomégalovirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à cytomégalovirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Cytomegalovirus Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Disease Models, Animal</term>
<term>Immune Tolerance</term>
<term>Macaca fascicularis</term>
<term>Transplant Recipients</term>
<term>Virus Activation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Activation virale</term>
<term>Animaux</term>
<term>Macaca fascicularis</term>
<term>Modèles animaux de maladie humaine</term>
<term>Receveurs de transplantation</term>
<term>Tolérance immunitaire</term>
</keywords>
</textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b>
</p>
<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.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<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.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<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.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b>
</p>
<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 T cells proliferated during CMV viremia.</p>
</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31385931</PMID>
<DateCompleted><Year>2020</Year>
<Month>09</Month>
<Day>29</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>09</Month>
<Day>29</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1534-6080</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>104</Volume>
<Issue>2</Issue>
<PubDate><Year>2020</Year>
<Month>02</Month>
</PubDate>
</JournalIssue>
<Title>Transplantation</Title>
<ISOAbbreviation>Transplantation</ISOAbbreviation>
</Journal>
<ArticleTitle>Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.</ArticleTitle>
<Pagination><MedlinePgn>270-279</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1097/TP.0000000000002893</ELocationID>
<Abstract><AbstractText Label="BACKGROUND">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.</AbstractText>
<AbstractText Label="METHODS">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.</AbstractText>
<AbstractText Label="RESULTS">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.</AbstractText>
<AbstractText Label="CONCLUSIONS">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 T cells proliferated during CMV viremia.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alonso-Guallart</LastName>
<ForeName>Paula</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Duran-Struuck</LastName>
<ForeName>Raimon</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pathobiology, University of Pennsylvania, Philadelphia, PA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zitsman</LastName>
<ForeName>Jonah S</ForeName>
<Initials>JS</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sameroff</LastName>
<ForeName>Stephen</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pereira</LastName>
<ForeName>Marcus</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stern</LastName>
<ForeName>Jeffrey</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Berglund</LastName>
<ForeName>Erik</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Llore</LastName>
<ForeName>Nathaly</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pierre</LastName>
<ForeName>Genevieve</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lopes</LastName>
<ForeName>Emily</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kofman</LastName>
<ForeName>Sigal B</ForeName>
<Initials>SB</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Danton</LastName>
<ForeName>Makenzie</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sondermeijer</LastName>
<ForeName>Hugo P</ForeName>
<Initials>HP</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Physiology, Maastricht University, Maastricht, Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Woodland</LastName>
<ForeName>David</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kato</LastName>
<ForeName>Yojiro</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ekanayake-Alper</LastName>
<ForeName>Dilrukshi K</ForeName>
<Initials>DK</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Iuga</LastName>
<ForeName>Alina C</ForeName>
<Initials>AC</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Cell Biology, Columbia University, New York, NY.</Affiliation>
</AffiliationInfo>
</Author>
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   |texte=   Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.
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Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.

Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.

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