Comment[ArrayExpressAccession] E-GEOD-35460 Public Release Date 2012-07-09 Investigation Title Gene expression profiling data from sooty mangabeys treated with interferon alpha Comment[Submitted Name] Gene expression profiling data from sooty mangabeys treated with interferon alpha Experiment Description In contrast to pathogenic HIV and SIV infection of humans and macaques, SIV infection of sooty mangabeys (SMs) is typically non-pathogenic despite high virus replication. A key feature of primary SIV infection of SMs is a strong type I interferon (IFN-I) response, characterized by massive up-regulation of interferon-stimulated genes (ISG), followed by rapid resolution during the acute-to-chronic phase transition and establishment of an immune quiescent state that persists throughout the chronic infection. Based on these observations we hypothesized that low levels of IFN-I signaling may be instrumental in preventing chronic immune activation and disease progression in SIV-infected SMs. We used microarrays to characterize gene expression changes induced by IFNalpha treatment. To directly assess the effects of an experimentally-induced augmentation of IFN-I signaling in chronically SIV-infected SMs, we administered recombinant rhesus macaque IFNalpha2-IgFc (rmIFNα2) to eight naturally SIV-infected SMs weekly for 16 weeks and longitudinally monitored viral load, lymphocyte counts, immune activation, SIV-specific CD8+ T-cell responses, and gene expression profile. Administration of rmIFNα2 was bioactive in vivo with gene expression profiling revealing a strong upregulation of numerous ISGs in the blood of treated animals. Date of Experiment Term Source Name EFO Term Source Version Term Source File http://www.ebi.ac.uk/efo/efo.owl Person Last Name Tharp Vanderford Silvestri Bosinger Villinger Schlicter Lawson Rend Tharp Person First Name Gregory Thomas Guido Steven Francois Chloe Benton Obaede Greg Person Mid Initials K H E O K Person Email gktharp@emory.edu Person Affiliation Yerkes National Primate Research Center Person Phone Person Fax Person Address Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, 954 Gatewood Dr, Atlanta, GA, USA Person Roles submitter Person Roles Term Source REF Person Roles Term Accession Number Normalization Type Normalization Term Accession Number Normalization Term Source REF Replicate Type Replicate Term Accession Number Replicate Term Source REF Experimental Design Experimental Design Term Accession Number Experimental Design Term Source REF Quality Control Type Quality Control Term Accession Number Quality Control Term Source REF Protocol Name P-GSE35460-1 P-GSE35460-6 P-GSE35460-3 P-GSE35460-8 P-GSE35460-7 P-GSE35460-2 P-GSE35460-4 P-GSE35460-5 Protocol Description ID_REF =
VALUE = Log2 scale of signal intensity after RMA normalization and summarization. Following fragmentation, 20 micrograms of cRNA were diluted into 300 microlitres of hybridization cocktail, with 200 microlitres hybridized for 16 hr at 45 C on GeneChip Rhesus Macaque Genome Array in Affymetrix Hybridization Oven 640. GeneChips were washed and stained in the Affymetrix Fluidics Station 450. N/A Data from .CEL files were uploaded to the RACE Bioconductor utility to perform RMA normalization. RACE normalized files were uploaded and analyzed using Partek Genomics Suite. GeneChips were scanned using the Affymetrix GeneChip Scanner 3000 7G. SIV+ Sooty mangabey monkeys were injected with 500,000 units subcutaneously with recombinant rhesus macaque IFNalpha2-IGFC fusion protein every week for 16 weeks. Whole blood was drawn into PAXgene tubes and stored at -80, samples were purified using standard Paxgene purification with QIAshredder columns and on-column DNAse digestion. 0.5 micrograms of total RNA was labeled using a modified version of the Affymetrix IVT Express protocol, incorporating blocking PNA oligos specific for rhesus & mangabey hemoglobin into the initial reverse transcription step, as reported in Taaffe et al. 2009 J Med Primatol and Bosinger et al. J Clin Invest 2009. Protocol Software Protocol Hardware Protocol Contact Protocol Type bioassay_data_transformation hybridization grow feature_extraction image_aquisition specified_biomaterial_action nucleic_acid_extraction labeling Protocol Term Source REF Protocol Term Accession Number Experimental Factor Name TREATMENT SUBJECT TIME Experimental Factor Type treatment subject time Experimental Factor Term Source REF Experimental Factor Term Accession Number Publication Title Treatment of SIV-infected sooty mangabeys with a type-I IFN agonist results in decreased virus replication without inducing hyperimmune activation. Publication Author List Vanderford TH, Slichter C, Rogers KA, Lawson BO, Obaede R, Else J, Villinger F, Bosinger SE, Silvestri G PubMed ID 22550346 Publication DOI 10.1182/blood-2012-02-411496 Publication Status Publication Status Term Source REF Publication Status Term Accession Number Comment[SecondaryAccession] GSE35460 Comment[GEOLastUpdateDate] 2012-07-09 Comment[AEExperimentType] transcription profiling by array Comment[GEOReleaseDate] 2012-07-08 Comment[ArrayExpressSubmissionDate] 2012-01-31 SDRF File E-GEOD-35460.sdrf.txt