{"doi":"10.1101/2021.04.16.440168","title":"MHC-matched allogeneic bone marrow transplants fail to eliminate SHIV-infected cells from ART-suppressed Mauritian cynomolgus macaques","abstract":"Abstract Background 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 but may include pre-transplant conditioning regimens, ART-mediated protection of donor cells, and graft-versus-host (GvH) responses. 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. Results We infected four MCMs with CCR5-tropic SHIV162P3 and started ART 6-16 weeks post-infection (p.i.) to establish robust viral reservoirs. We maintained the MCMs on continuous ART during myeloablative conditioning with total body irradiation (TBI) and while transplanting allogeneic MHC-matched α/β T cell-depleted bone marrow cells. Post-transplant, we prophylactically treated the MCMs with cyclophosphamide and tacrolimus to prevent GvH disease (GvHD). The transplants produced ~85% whole blood donor chimerism without causing high-grade GvHD. Consequently, three MCMs had undetectable SHIV DNA in their peripheral blood mononuclear cells post-transplant. However, SHIV-harboring cells persisted in various tissues. We detected viral DNA in lymph node biopsies and terminal analyses of tissues between 38 and 62 days post-transplant. Further, we removed ART from one MCM at 63 days post-transplant, resulting in viral rebound within seven days and viral loads nearing 1×10 8 SHIV RNA copies/ml of plasma after treatment interruption. Conclusions Our results indicate that myeloablative conditioning and maintaining ART through the peri-transplant period alone are insufficient for eradicating latent viral reservoirs early after allo-HSCTs. Furthermore, our findings suggest that extended ART and GvH responses may be necessary to substantially deplete viral reservoirs after allo-HSCTs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":223916,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":454713,"name":"Saritha S. D’Souza","orcid":"0000-0002-9827-9622","position":1,"is_corresponding":false},{"id":540697,"name":"Lea M. Matschke","orcid":"0000-0003-4243-9292","position":2,"is_corresponding":false},{"id":532230,"name":"Sarah Bennett","orcid":"0000-0002-4605-2776","position":3,"is_corresponding":false},{"id":532231,"name":"Laurel Kelnhofer-Millevolte","orcid":"0000-0002-1635-1222","position":4,"is_corresponding":false},{"id":380630,"name":"Kran Suknuntha","orcid":"0000-0002-6648-8235","position":5,"is_corresponding":false},{"id":454712,"name":"Akhilesh Kumar","orcid":"0000-0003-2757-5181","position":6,"is_corresponding":false},{"id":484963,"name":"Jennifer Coonen","orcid":"0000-0001-5403-3412","position":7,"is_corresponding":false},{"id":277448,"name":"Christian M. Capitini","orcid":"0000-0002-2276-6731","position":8,"is_corresponding":false},{"id":277447,"name":"Peiman Hematti","orcid":"0000-0001-5836-4497","position":9,"is_corresponding":false},{"id":350727,"name":"Thaddeus G. Golos","orcid":"0000-0002-7897-4337","position":10,"is_corresponding":false},{"id":364076,"name":"Igor I. Slukvin","orcid":"0000-0001-9693-6927","position":11,"is_corresponding":false},{"id":532233,"name":"Matthew R. Reynolds","orcid":"0000-0002-1484-6408","position":12,"is_corresponding":false},{"id":532232,"name":"Jason T. Weinfurter","orcid":"0000-0001-8076-2598","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T23:54:14.760456Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}