Abdel-Mohsen, Mohamed

Deeks, Steven G

Deng, Xutao

Pilcher, Christopher D

Pillai, Satish K

Trypsteen, Wim

Vandekerckhove, Linos

Ghent University Academic Bibliography

Transcriptomic correlates of HIV reservoir size during antiretroviral therapyWim Trypsteen1, Mohamed Abdel-Mohsen2,3, Xutao Deng3,4, Christopher D. Pilcher4, Steven G. Deeks4, Linos Vandekerckhove1, Satish K. Pillai3,41HIV Cure Research Center, Ghent University, Belgium; 2Vaccine and Immunotherapy, Wistar Institute, Philadelphia, PA, USA; 3Vitalant Research Institute, San Francisco, CA, USA; 4University of California, San Francisco, CA, USACROI Meeting, Seattle, USA (4-7 March 2019)Poster ID: 0332 @ Session P-E01 (03/05/2019)HIV Cure Research Centerwww.hcrc.ugent.beResultssatish.pillai@ucsf.eduwim.trypsteen@ugent.beHIV therapy (ART)HIVT cellenHIVHealthy individual HIV infectionLatent HIVBackground• HIV is an intracellular pathogen that hijacks the cellular machinery• HIV causes a persistent infection under antiretroviral treatment• Clues for HIV cure approaches lay In the transcriptome of HIV infected cellsHIV markers HostPlasmaTreatment initiation:2.74 years (2.11-3.36)Time on treatment:1.61 years (1.56-1.67)MethodsGoalExamine transcriptome of CD4 T cells in search of host gene expression signatures involved in HIV persistenceTranscriptome correlates per markerMean (CI)Viral load 0.24 (0.17-0.31)TxInitiation (Years) 2.74 (2.11-3.36)TxTime (Years) 1.61 (1.56-1.67)HIV RNA 1906.22 (1436.81-2375.63)HIV DNA: Pol 807.17(492.07-1122.27)HIV DNA: 2 LTR 94.10 (54.21-133.99)ConclusionHIV patient characteristics and quantification of HIV markers• This study reveals associations between  host genetic pathways and HIV persistence• Especially HIV RNA levels were correlated with following pathways: Notch, p53 pathway, RIG-I and EDG1-induced T cell exhaustion• HIV DNA levels correlated with PDCD1 and ST3GAL5 genes which indicate clonal proliferation as hallmark of HIV persistence • Treatment initiation was associated with pathways useful for immunotherapy: p53, mTOR• Genes with RNAseq counts >10 Reads Per Kilobase Million across samples  were analyzed: 9543 genes expressed• CD4+ T cell transcriptomes were correlated with reservoir markers and  ART initiation timing in a guilt-by-association manner and involved the construction of correlation matrices (Pearson) with subsequent gene set enrichment analysis• Significance was determined using a False Discovery Rate adjusted p-value (q-value) cutoff of 0.05. Gene sets were retrieved from the molecular signature databases: BIOCARTA, KEGG and REACTOME0332Signal: 141 genesSignal: 5 genes Signal: 469 genesSignal: 1 geneTop correlated gene Transcriptome signalPearson: 0.65qval: 0.011Pearson: 0.57qval: 0.0016Pearson: 0.62qval: 0.0006Pearson: 0.57qval: 0.003HIV 2LTR HIV DNA (Pol) HIV RNA Treatment InitiationGene Set Enrichment Analysis HIV RNATMEM43PDCD1ST3GAL5PIP4K2CAPOBEC3G/F0 1 51414690Correlated genes (#)Correlation AnalysisHIV 2LTRTMEM43HIV DNA (Pol)PDCD1HIV RNAMARK3TxInitCOX6CViral load: log(copies)/mL plasmaHIV RNA, DNA & 2LTR: copies/106 PBMCs

Transcriptomic correlates of HIV reservoir size during antiretroviral therapy

https://biblio.ugent.be/publication/8612765/file/8612766.pdf

Transcriptomic correlates of HIV reservoir size during antiretroviral therapy

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Ghent University Academic Bibliography