Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques
Issued Date
2022-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85134413904
Pubmed ID
35853970
Journal Title
Scientific Reports
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.12 No.1 (2022)
Suggested Citation
Weinfurter J.T., D’Souza S.S., Matschke L.M., Bennett S., Kelnhofer-Millevolte L.E., Suknuntha K., Kumar A., Coonen J., Capitini C.M., Hematti P., Golos T.G., Slukvin I.I., Reynolds M.R. Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques. Scientific Reports Vol.12 No.1 (2022). doi:10.1038/s41598-022-16306-z Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86408
Title
Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques
Author's Affiliation
University of Wisconsin-Madison
University of Wisconsin School of Medicine and Public Health
University of Wisconsin School of Veterinary Medicine
UW Health
Faculty of Medicine Ramathibodi Hospital, Mahidol University
University of Wisconsin Carbone Cancer Center
Wisconsin National Primate Research Center
University of Wisconsin School of Medicine and Public Health
University of Wisconsin School of Veterinary Medicine
UW Health
Faculty of Medicine Ramathibodi Hospital, Mahidol University
University of Wisconsin Carbone Cancer Center
Wisconsin National Primate Research Center
Other Contributor(s)
Abstract
Allogeneic hematopoietic stem cell transplants (allo-HSCTs) dramatically reduce HIV reservoirs in antiretroviral therapy (ART) suppressed individuals. However, the mechanism(s) responsible for these post-transplant viral reservoir declines are not fully understood. Therefore, we modeled allo-HSCT in ART-suppressed simian-human immunodeficiency virus (SHIV)-infected Mauritian cynomolgus macaques (MCMs) to illuminate factors contributing to transplant-induced viral reservoir decay. Thus, we infected four MCMs with CCR5-tropic SHIV162P3 and started them on ART 6–16 weeks post-infection (p.i.), maintaining continuous ART during myeloablative conditioning. To prevent graft-versus-host disease (GvHD), we transplanted allogeneic MHC-matched α/β T cell-depleted bone marrow cells and prophylactically treated the MCMs with cyclophosphamide and tacrolimus. The transplants produced ~ 85% whole blood donor chimerism without causing high-grade GvHD. Consequently, three MCMs had undetectable SHIV DNA in their blood post-transplant. However, SHIV-harboring cells persisted in various tissues, with detectable viral DNA in lymph nodes and tissues between 38 and 62 days post-transplant. Further, removing one MCM from ART at 63 days post-transplant resulted in SHIV rapidly rebounding within 7 days of treatment withdrawal. In conclusion, transplanting SHIV-infected MCMs with allogeneic MHC-matched α/β T cell-depleted bone marrow cells prevented high-grade GvHD and decreased SHIV-harboring cells in the blood post-transplant but did not eliminate viral reservoirs in tissues.