1. Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques.
- Author
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Weinfurter JT, D'Souza SS, Matschke LM, Bennett S, Kelnhofer-Millevolte LE, Suknuntha K, Kumar A, Coonen J, Capitini CM, Hematti P, Golos TG, Slukvin II, and Reynolds MR
- Subjects
- Animals, Bone Marrow Transplantation adverse effects, HIV, Humans, Macaca fascicularis, Receptors, Antigen, T-Cell, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, HIV Infections, Hematopoietic Stem Cell Transplantation adverse effects, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus genetics
- 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., (© 2022. The Author(s).)
- Published
- 2022
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