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| Status |
Public on Jan 08, 2024 |
| Title |
TGF-beta blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo [scRNA-seq] |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing of the anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirmed the latency reversal properties of in vivo TGF-beta blockade, decreased viral reservoirs and stimulated immune responses. Eight SIV-infected macaques on suppressive ART were treated with 4 2-week cycles of galunisertib. ART was discontinued 3 weeks after the last dose, and macaques euthanized 6 weeks after ART-interruption(ATI). One macaque did not rebound, while the remaining rebounded between week 2 and 6 post-ATI. Galunisertib led to viral reactivation as indicated by plasma viral load and immunoPET/CT with the 64Cu-DOTA-F(ab')2-p7D3-probe. Half to 1 Log decrease in cell-associated (CA-)SIV DNA was detected in lymph nodes, gut and PBMC, while intact pro-virus in PBMC decreased by 3-fold. No systemic increase in inflammatory cytokines was observed. High-dimensions cytometry, bulk and single-cell RNAseq revealed a shift toward an effector phenotype in T and NK cells.
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| Overall design |
To clarify the impact of galunisertib at the single cell level and in lymphoid tissues, we also performed scRNAseq analysis of cells isolated from LNs before (right axillar) and after (right or left inguinal) the first cycle.
8 Macaques, 2 time points Before and After Galunisertib.
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| Contributor(s) |
Kim J, Bose D, Aranga M, Haque M, Fennessey C, Caddell R, Thomas Y, Ferrell D, Ali S, Grody E, Goyal Y, Cicala C, Arthos J, Keele B, Vaccari M, Lorenzo-Redondo R, Hope T, Villinger F, Martinelli E |
| Citation(s) |
38355731 |
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| Submission date |
Oct 07, 2023 |
| Last update date |
Feb 26, 2024 |
| Contact name |
Jinhee Kim |
| E-mail(s) |
jinhee.kim@northwestern.edu
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| Organization name |
Northwestern University
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| Department |
Infectious Disease
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| Lab |
Martinelli
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| Street address |
676 North St. Clair Street Arkes Suite 2330
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
| GPL27943 |
Illumina NovaSeq 6000 (Macaca mulatta) |
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| Samples (1) |
| GSM7831037 |
Lymph node, 8 macaques, Before and After Galunisertib |
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| This SubSeries is part of SuperSeries: |
| GSE244871 |
TGF-beta blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo |
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| Relations |
| BioProject |
PRJNA1025242 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE244870_RAW.tar |
611.7 Mb |
(http)(custom) |
TAR (of CSV, MTX, XLSX) |
SRA Run Selector |
| Raw data are available in SRA |
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