Autopsy Study Defines Composition and Dynamics of the HIV-1 Reservoir after Allogeneic Hematopoietic Stem Cell Transplantation with CCR5Δ32/Δ32 Donor Cells

Autor: Laura E. P. Huyveneers, Anke Bruns, Arjen Stam, Pauline Ellerbroek, Dorien de Jong, Noémi A. Nagy, Stephanie B. H. Gumbs, Kiki Tesselaar, Kobus Bosman, Maria Salgado, Gero Hütter, Lodewijk A. A. Brosens, Mi Kwon, Jose Diez Martin, Jan T. M. van der Meer, Theun M. de Kort, Asier Sáez-Cirión, Julian Schulze zur Wiesch, Jaap Jan Boelens, Javier Martinez-Picado, Jürgen H. E. Kuball, Annemarie M. J. Wensing, Monique Nijhuis
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Viruses, Vol 14, Iss 9, p 2069 (2022)
Druh dokumentu: article
ISSN: 14092069
1999-4915
74048228
DOI: 10.3390/v14092069
Popis: Allo-HSCT with CCR5Δ32/Δ32 donor cells is the only curative HIV-1 intervention. We investigated the impact of allo-HSCT on the viral reservoir in PBMCs and post-mortem tissue in two patients. IciS-05 and IciS-11 both received a CCR5Δ32/Δ32 allo-HSCT. Before allo-HSCT, ultrasensitive HIV-1 RNA quantification; HIV-1-DNA quantification; co-receptor tropism analysis; deep-sequencing and viral characterization in PBMCs and bone marrow; and post-allo-HSCT, ultrasensitive RNA and HIV-1-DNA quantification were performed. Proviral quantification, deep sequencing, and viral characterization were done in post-mortem tissue samples. Both patients harbored subtype B CCR5-tropic HIV-1 as determined genotypically and functionally by virus culture. Pre-allo-HSCT, HIV-1-DNA could be detected in both patients in bone marrow, PBMCs, and T-cell subsets. Chimerism correlated with detectable HIV-1-DNA LTR copies in cells and tissues. Post-mortem analysis of IciS-05 revealed proviral DNA in all tissue biopsies, but not in PBMCs. In patient IciS-11, who was transplanted twice, no HIV-1-DNA could be detected in PBMCs at the time of death, whereas HIV-1-DNA was detectable in the lymph node. In conclusion, shortly after CCR5Δ32/Δ32, allo-HSCT HIV-1-DNA became undetectable in PBMCs. However, HIV-1-DNA variants identical to those present before transplantation persisted in post-mortem-obtained tissues, indicating that these tissues play an important role as viral reservoirs.
Databáze: Directory of Open Access Journals
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