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of California San Diego, et al."],"cell_type":["CL:0000624 CD4-positive, alpha-beta T cell"],"repository":["GPMDB"],"pubmed_abstract":["Suberoylanilide hydroxamic acid (SAHA) has been assessed in clinical trials as part of a \"shock and kill\" strategy to cure HIV-infected patients. While it was effective at inducing expression of HIV RNA (\"shock\"), treatment with SAHA did not result in a reduction of reservoir size (\"kill\"). We therefore utilized a combined analysis of effects of SAHA on the host transcriptome and proteome to dissect its mechanisms of action that may explain its limited success in \"shock and kill\" strategies. CD4+ T cells from HIV seronegative donors were treated with 1μM SAHA or its solvent dimethyl sulfoxide (DMSO) for 24h. Protein expression and post-translational modifications were measured with iTRAQ proteomics using ultra high-precision two-dimensional liquid chromatography-tandem mass spectrometry. Gene expression was assessed by Illumina microarrays. Using limma package in the R computing environment, we identified 185 proteins, 18 phosphorylated forms, 4 acetylated forms and 2982 genes, whose expression was modulated by SAHA. A protein interaction network integrating these 4 data types identified the HIV transcriptional repressor HMGA1 to be upregulated by SAHA at the transcript, protein and acetylated protein levels. Further functional category assessment of proteins and genes modulated by SAHA identified gene ontology terms related to NFκB signaling, protein folding and autophagy, which are all relevant to HIV reactivation. In summary, SAHA modulated numerous host cell transcripts, proteins and post-translational modifications of proteins, which would be expected to have very mixed effects on the induction of HIV-specific transcription and protein function. Proteome profiling highlighted a number of potential counter-regulatory effects of SAHA with respect to viral induction, which transcriptome profiling alone would not have identified. These observations could lead to a more informed selection and design of other HDACi with a more refined targeting profile, and prioritization of latency reversing agents of other classes to be used in combination with SAHA to achieve more potent induction of HIV expression."],"pubmed_title":["Mixed effects of suberoylanilide hydroxamic acid (SAHA) on the host transcriptome and proteome and their implications for HIV reactivation from latency."],"pubmed_authors":["White Cory H CH,Johnston Harvey E HE,Moesker Bastiaan B,Manousopoulou Antigoni A,Margolis David M DM,Richman Douglas D DD,Spina Celsa A CA,Garbis Spiros D SD,Woelk Christopher H CH,Beliakova-Bethell Nadejda N,","White Cory H CH, Johnston Harvey E HE, Moesker Bastiaan B, Manousopoulou Antigoni A, Margolis David M DM, Richman Douglas D DD, Spina Celsa A CA, Garbis Spiros D SD, Woelk Christopher H CH, Beliakova-Bethell Nadejda N"],"name_synonyms":["Acquired Immune Deficiency Syndrome Virus, host organism, Human T-Cell Lymphotropic Virus Type III, Human T-Lymphotropic Virus Type III, Human Immunodeficiency Virus, Transcriptome, Human T Lymphotropic Virus Type III, Lymphadenopathy-Associated, Viruses, AIDS Viruses, Transcriptome Profile, Profile, Expression Profiles, AIDS Virus, Gene Expression Profile, HTLV-III, Gene, Immunodeficiency Viruses, Profiles, Lymphadenopathy-Associated Virus., Human T Cell Leukemia Virus Type III, Signatures, LAV-HTLV-III, Human Immunodeficiency, Human, whole transcriptome, Gene Expression, Lymphadenopathy Associated Virus, AIDS, Expression Signature, Gene Expression Profiles, Immunodeficiency Virus, Expression Signatures, Gene Expression Signatures, Acquired Immunodeficiency Syndrome Virus, Transcriptomes, Virus, Lymphadenopathy-Associated Viruses, HIV, Gene Expression Signature, Signature, Human T-Cell Leukemia Virus Type III, Human Immunodeficiency Viruses, Expression Profile, Proteomes, Human T Cell Lymphotropic Virus Type III, AIDS virus, Transcriptome Profiles"],"description_synonyms":["Dimethyl, Methane, host organism, Human T-Cell Lymphotropic Virus Type III, DIMETHYL SULFOXIDE, PLXN5, T-cell surface antigen T4/Leu-3, determination, Tandem, Transcriptome Profile, Circulatory, Nl1, AIDS Virus, Gene Expression Profile, HTLV-III, Gene, dimethylsulfoxyde, PLEXIN-B1, Rimso 100, Profiles, C2H6OS, Failure, Human Immunodeficiency, SeP, Circulatory Collapse, Human, Lymphadenopathy Associated Virus, L3T4, Sulphoxide, CEH, Ly-4, Virus, NEPII, NL1, NL2, SEH, Human T-Cell Leukemia Virus Type III, Rheumabene, SEP, S(O)Me2, Shock, sulfinylbis(methane), Human T-Lymphotropic Virus Type III, Viruses, Profile, dimethyl sulphoxide, Immunodeficiency Viruses, proteins, Mass Spectrometry, Human T Cell Leukemia Virus Type III, Signatures, sEP, Hypovolemic Shock, Rimso-50, dimetil sulfoxido, Hypovolemic, Dimethylsulphinyl, Rimso, Dimethylsulfoxide, Expression Signature, SELP, Transcriptomes, Lymphadenopathy-Associated Viruses, Mass Spectrometry Mass Spectrometry., HIV, Human Immunodeficiency Viruses, Dimethylsulfoxid, Lymphadenopathy-Associated Virus, sulfinylbis-, data, Human Immunodeficiency Virus, DMSO, Transcriptome, Human T Lymphotropic Virus Type III, dimethyli sulfoxidum, T-cell surface antigen T4|Leu-3, dmso, Expression Profiles, methylsulfinylmethane, Liquid Chromatography, Mell1, Circulatory Failure, Cell, whole transcriptome, Gene Expression, polypeptide, (CH3)2SO, AIDS, MMEL2, T-cell differentiation antigen L3T4, Dimexide, Immunodeficiency Virus, Expression Signatures, Dimethylsulphoxide, chemical analysis, Gene Expression Signatures, Gene Expression Signature, Dimethyl sulfoxide, Sulfoxide, Sulfinylbis(methane), Expression Profile, AIDS virus, Transcriptome Profiles, Rimso 50, Acquired Immune Deficiency Syndrome Virus, (methanesulfinyl)methane, Lymphadenopathy-Associated, AIDS Viruses, Rimso50, T-cell surface glycoprotein CD4, Sclerosol, dimethyl sulfoxide, Dimethyl Sulphoxide, CD4mut, Mass Spectrometry-Mass Spectrometry, LAV-HTLV-III, Collapse, Gene Expression Profiles, Acquired Immunodeficiency Syndrome Virus, CD4, Eph2, assay, Signature, dimethyl sulfur oxide, Proteomes, Human T Cell Lymphotropic Virus Type III, NEP2"],"pubmed_title_synonyms":["Acquired Immune Deficiency Syndrome Virus, host organism, Human T-Cell Lymphotropic Virus Type III, Human T-Lymphotropic Virus Type III, Human Immunodeficiency Virus, Transcriptome, Human T Lymphotropic Virus Type III, Lymphadenopathy-Associated, Viruses, AIDS Viruses, Transcriptome Profile, Profile, Expression Profiles, AIDS Virus, Gene Expression Profile, HTLV-III, Gene, Immunodeficiency Viruses, Profiles, Lymphadenopathy-Associated Virus., Human T Cell Leukemia Virus Type III, Signatures, LAV-HTLV-III, Human Immunodeficiency, Human, whole transcriptome, Gene Expression, Lymphadenopathy Associated Virus, AIDS, Expression Signature, Gene Expression Profiles, Immunodeficiency Virus, Expression Signatures, Gene Expression Signatures, Acquired Immunodeficiency Syndrome Virus, Transcriptomes, Virus, Lymphadenopathy-Associated Viruses, HIV, Gene Expression Signature, Signature, Human T-Cell Leukemia Virus Type III, Human Immunodeficiency Viruses, Expression Profile, Proteomes, Human T Cell Lymphotropic Virus Type III, AIDS virus, Transcriptome Profiles"],"pubmed_abstract_synonyms":["Methane, liquid chromatography tandem mass spectroscopy, host organism, Human T-Cell Lymphotropic Virus Type III, Ribonucleic, DIMETHYL SULFOXIDE, Materials, Gene Ontology Projects, T-cell surface antigen T4/Leu-3, determination, Globular Protein Folding, selection process, AIDS Virus, Gene Expression Profile, Profiles, beta-tubulin folding, Human Immunodeficiency, Circulatory Collapse, Lymphadenopathy Associated Virus, autophagy, L3T4, Autophagic Cell Deaths, Cellular Autophagies, Virus, Ly-4, Project, Impacts, HMGA1A, Environmental Impacts, Non Polyadenylated, Rheumabene, RNA Gene Products, Shock, treatment, Hmga1a, LCMSMS, Gene Expressions, Autophagies, Macro autophagy, dimethyl sulphoxide, Macro-autophagies, proteins, number of, Signatures, Hmga1b, Folding, chaperonin-mediated tubulin folding, Environmental Impact, DNA-dependent, Dimethylsulfoxide, Expression Signature, signaling process, disease management, Transcriptomes, [Pb], Dimethylsulfoxid, single organism signaling, LC-MS2, sulfinylbis-, DMSO, HMGIY, plomo, dimethyli sulfoxidum, Autophagic, T-cell surface antigen T4|Leu-3, dmso, DNA-dependent transcription, ribose nucleic acid, Expression Profiles, methylsulfinylmethane, ribonucleic acids, LC-MS/MS, Blei, plomb, 82Pb, Circulatory Failure, extra or missing physical or functional parts, INSDC_feature:misc_RNA, Autophagic Cell, Gene Expression, chaperone activity, (CH3)2SO, Globular Protein, co-chaperonin activity, AIDS, Ribonukleinsaeure, Expression Signatures, Autophagic Programmed Cell Death, Autophagocytosis, pentosenucleic acids, Genetic Materials, Cellular, Autophagic Cell Death, Ontology Projects, alpha-tubulin folding, Ribonucleic acids, Protein Foldings, Sulfinylbis(methane), Expression Profile, Hmgiy, Genetic Material, Transcriptome Profiles, Rimso 50, Acquired Immune Deficiency Syndrome Virus, Acid, Gene Ontologies, (methanesulfinyl)methane, Ontology, Lymphadenopathy-Associated, Ontologies, Projects, Rimso50, Autophagy, T-cell surface glycoprotein CD4, CD4mut, Cell Death, Hmgi, co-chaperone activity, Globular Protein Foldings, Patient, Material, liquid chromatography-tandem mass spectroscopy, Acquired Immunodeficiency Syndrome Virus, multichaperone pathway, Cistron, Hmgy, Proteomes, Dimethyl, protein levels, transcription, biological signaling, Transcriptome Profile, Circulatory, Macroautophagy, Foldings, number, lead atom, HTLV-III, Gene, dimethylsulfoxyde, Rimso 100, C2H6OS, InChI=1/Pb, Gene Ontology Project, Failure, Gene Ontology, LC-MS-MS, Human, Sulphoxide, chaperonin ATPase activity, LC-MSMS, Gene Products, Cellular Autophagy, non-chaperonin molecular chaperone ATPase 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III"],"view_count":["15"],"citation_count":["0"],"search_count":["5"],"full_dataset_link":["http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310023592"],"search_domains":["dbgap_ncbi~0","patentfamilies~0","rfam~0","merops~0","complex-portal~0","uniprot~0","wormbaseparasite~0","embl-covid19~0","reactome~0","emdb~0","wgs_masters~0","ebiweb_resources~0","opentargets_genetics~0","biomodels_all~0","ipd-mhc~0","ebiweb_teams~0","taxonomy~0","genome_assembly~0","sc-experiments~0","ebiweb_people~0","enzymeportal_enzymes~0","ipd-nhkir~0","cellosaurus~0","pdbe~0","chebi~0","patentproteins~0","interpro7~0","uniref~0","chembl~0","pdbekb~0","gpcrdb~0","hgnc~0","sc-genes~0","intact~0","rhea~0","ebiweb_training~0","alphafold~0","imgt-hla~0","patentnucleotides~0","ensemblroot~0","eva_studies~0","non-coding~0","europepmc~0","pubmed~1","identifiers_registry~0","pdbechem~0","hpa-covid19~0","eva-variants-covid19~0","biosamples~0","gwas_catalog~0","biotools~0","tls_masters~0","mesh~0","coding~0","sra~0","opentargets~0","efo~0","embl-pathogen~0","project~0","pride~1","human_diseases~0","geo_datasets~0","embl~0","treefam~0","uniparc~0","ols~0","dgva~0","intenz~0","go~0","tsa_masters~0","biosamples-covid19~0","ebiweb_corporate~0","omim~0","lrg~0","earlycause-molecular-sequences~0","ipd-kir~0","empiar~0","rnacentral~0","orcid_data_claims~0","gpmdb~2","lineage-covid19~0","metagenomics~0","pfam~0","pride archive~1","varsite~0"],"reanalysis_count":["0"],"submitter_keywords":["Resource Reanalysis"],"citation_count_scaled":["0.0"],"reanalysis_count_scaled":["0.0"],"view_count_scaled":["0.0046267735965453425"],"download_count_scaled":["0.0"],"normalized_connections":["1.0"],"additional_accession":[]},"is_claimable":false,"name":"Mixed effects of suberoylanilide hydroxamic acid (SAHA) on the host transcriptome and proteome and their implications for HIV reactivation from latency.","description":"Data from ProteomeXchange, PXD ID: PXD002150. File: 14july14_saha_b_65.mzml. Published as part of Antiviral Res. 2015 Sep 3. pii: S0166-3542(15)00213-2  . From the Abstract: {{i}} ... We therefore utilized a combined analysis of effects of SAHA on the host transcriptome and proteome to dissect its mechanisms of action that may explain its limited success in shock and kill strategies. CD4+ T cells from HIV seronegative donors were treated with 1 μM SAHA or its solvent dimethyl sulfoxide (DMSO) for 24 hours. Protein expression and post-translational modifications were measured with iTRAQ proteomics using ultra high-precision two-dimensional liquid chromatography - tandem mass spectrometry ... {{/i}}","dates":{"submission":"2015-09-12"},"accession":"GPM32310023592","cross_references":{"pubmed":["26343910"],"Pride":["PXD002150"],"pride":[],"Pride Archive":["PXD002150"]}}