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Series GSE203603 Query DataSets for GSE203603
Status Public on Aug 30, 2023
Title Peripheral Blood Biomarkers in ART-Suppressed, SIV-Infected Rhesus Macaques Predict Viral Rebound Following ART Discontinuation
Organism Macaca mulatta
Experiment type Expression profiling by high throughput sequencing
Summary The development of biomarkers that can predict viral rebound following discontinuation of antiretroviral therapy (ART) in HIV-1-infected humans would be an important advance in HIV-1 cure research. In a prior study, we initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection prior to plasma viremia1. Following 6 months of suppressive ART, we discontinued ART and observed viral rebound in 9 of 20 animals. Here we show that transcriptomic and proteomic signatures of inflammation and immune activation in peripheral blood during ART suppression predicted viral rebound following ART discontinuation. Higher levels of proinflammatory and cellular immune activation pathways, including TNF, IL-1, IL-6, monocyte, and T cell activation signaling pathways, correlated with viral rebound following ART discontinuation. Immune modulatory IL-10 and TGF-b signaling also correlated with viral rebound. We then validated these candidate biomarkers of viral rebound in a second cohort of SIV-infected, ART-suppressed macaques. Taken together, these data suggest that persistent upregulation of inflammatory and immune activation pathways despite suppressive ART may represent a peripheral blood biomarker signature of the rebound-competent viral reservoir. The development of interventions that target the viral reservoir and modulate this signature may open new avenues in HIV-1 cure research.
Overall design We evaluated transcriptomic and proteomic features in peripheral blood and lymph nodes prior to ART discontinuation to identify potential biomarkers that predicted rebound viremia following ART discontinuation. We performed transcriptomic profiling in this cohort of 20 macaques at week 24 of ART suppression and showed that signatures in macaques that subsequently exhibited viral rebound following ART discontinuation (9 macaques) were different than signatures in macaques that did not rebound (11 macaques).
Web link
Contributor(s) Aid M, Colarusso A, Walker-Sperling V, Barouch DH
Citation(s) 37467721
Submission date May 23, 2022
Last update date Nov 29, 2023
Contact name Dan Barouch
Organization name BIDMC
Department CVVR
Lab Barouch Lab
Street address 3 Blackfan Circle
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL21120 Illumina NextSeq 500 (Macaca mulatta)
Samples (105)
GSM6176720 M6503, Blood, Baseline
GSM6176721 M6504, Blood, Baseline
GSM6176722 M6505, Blood, Baseline
BioProject PRJNA841577
SRA SRP376604

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Supplementary file Size Download File type/resource
GSE203603_geo_1511_may19_LN_countMatrix.csv.gz 1.1 Mb (ftp)(http) CSV
GSE203603_geo_1511_may19_PBMC_countMatrix.csv.gz 1.3 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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