SIV Vaccination Metagenome
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR906480_1.fastq.gz | Fastqsanger.gz | |||
| ERR906480_2.fastq.gz | Fastqsanger.gz | |||
| ERR906481_1.fastq.gz | Fastqsanger.gz | |||
| ERR906481_2.fastq.gz | Fastqsanger.gz |
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Project description:The 68-1 rhesus cytomegalovirus (RhCMV) vector which expresses Simian Immunodeficiency Virus (SIV) genes (Gag/Tat/Nef/5-Pol) is effective in controlling and clearing SIV in rhesus macaques and the human ortholog vector is a vaccine candidate for the prevention of HIV. Currently the RhCMV/SIV vaccine is only effective in ~55% (referred to as protected animals) of Rhesus Macaques. A previous study by Barrenäs et al., 2021, showed that significant gene expression changes in a key set of IL-15 linked genes was correlated with a protection outcome. To further our understanding of the transcriptomic state if cells in protected animals and mechanisms of protection induced by the RhCMV vaccine we performed single cell RNA-sequencing on PBMCs from protected, non-protected and unvaccinated animals at longitudinal time points post SIV challenge. We identified monocytes, CD8 T cells and NK cells were primarily responsible for expression of genes in the IL-15 enriched protective signature. Myeloid cells were transcriptionally distinct 1) from all other cell types, 2) between nonprotected and protected vaccinated RMs and 3) between protected and unvaccinated SIV-infected animals. Specifically, transcriptomics indicated that myeloid cells were more activated and mature in protected animals by the vaccine at pre-challenge and post-challenge time points. This suggests that the transcriptional state of myeloid cells is essential in eliciting a protection outcome and could be used to determine whether an animal will be protected after vaccination.
2025-08-01 | GSE291725 | GEO
Project description:Transcriptional Profiling Reveals Distinguishing Features of Immune Activation in the Lymphatic Tissues of Sooty Mangabeys and Rhesus Macaques in Early SIV Infection Immune activation in the chronic stages of HIV-1 and SIV infection of rhesus macaques is thought to play a critical role in CD4+ T cell depletion and progression to AIDS. Conversely, the lack of immune activation in the chronic stages of SIV infection of sooty mangabeys is thought to protect this species from a pathogenic outcome. This critical difference in immune activation in rhesus macaques and sooty mangabeys has recently been shown to be established in the early stages of SIV infection where there is immune activation in both species, but in sooty mangabeys immune activation is subsequently resolved. Here we report the results of a microarray analysis of early SIV infection in the lymphatic tissues of rhesus macaques and sooty mangabeys that provides a comprehensive view of the distinguishing features of immune activation and host defenses in the two species. We confirm immune activation in sooty mangabeys, but show that it is less robust than in rhesus macaques, where positive feedback loops involving cytosolic pattern recognition receptors, and chemokines and their ligands amplify the response to early SIV infection. We confirm resolution of immune activation in sooty mangabeys, but show it to be partial and selective, identifying the interferon system and CD38 as key correlates of outcome. We also identify potentially novel immunoregulatory mechanisms that mediate resolution, and defensins as host defenses sooty mangabeys employ as expression of other innate immune system effectors declines. The studies we report here were undertaken in a collaborative longitudinal analysis of early SIV infection in SMs described in Bosinger et al and previously reported studies (Estes et al., J Immunol 1008, 180, 6798-6807.). Briefly, SMs were inoculated i.v. with 1 ml of plasma from an experimentally SIVsmm-infected SM sampled at day 11 post infection, with a viral load 107 copies/ml. In our studies we analyzed axillary or inguinal lymph node biopsies that had been obtained from two SMs prior to infection; two SMs at the peak of viral replication at 14 dpi; and two SMs at 30 dpi as viral loads were decreasing to set point. We analyzed axillary or inguinal LNs from 4 RMs without SIV infection and LNs from four RMs infected intravaginally with 2x105 TCID50 of SIVmac239 and sacrificed at 14 dpi the peak of viral replication from two cross-sectional studies described in (Miller et al., The Journal of Virology 2005, 79, 9217-9227.). For lymph node (LN) biopsies, animals were anesthetized with Ketamine or Telazol; the skin over the axillary or inguinal region was clipped and surgically prepped. An incision was made over the LN, which was exposed by blunt dissection and excised over clamps. A portion of the lymph node biopsy for microarray analysis was snap frozen in liquid N2. All animals were housed and cared for at the Yerkes National Primate Research Center in Atlanta, Georgia in accordance with the regulations of the American Association of Accreditation of Laboratory Animal Care standards. These studies were approved by the Emory University and University of Pennsylvania Institutional Animal Care and Usage Committees (IACUC). Microarray Analysis RNA extractions, synthesis of biotin-labeled cRNA probes, microarray hybridization, and data analysis followed previously published procedures (Li et al., The Journal of infectious diseases 2004, 189, 572-582; Li et al., J Immunol 2009, 2009, 183: 1975–1982.). Briefly, snap-frozen lymph node was homogenized in TRIzol. Total RNA was isolated and further purified. Double stranded cDNA and biotin-labeled cRNA probes were synthesized, column purified and fragmented. Fifteen micrograms of fragmented cRNA was hybridized to an Affymetrix GeneChip® Rhesus Macaque Genome Array. After hybridization, chips were washed, stained with streptavidin-phycoerythrin, and scanned with GeneChip Operating Software at the Biomedical Genomics Center at the University of Minnesota. Preparation of cRNA probes and microarray hybridizations were done in duplicate for each RNA sample. Cel. files were uploaded into the Expressionist program (Genedata, Pro version 5.1) and the expression level for each of the 47,000 transcripts in the arrays were analyzed using the RMA algorithm. The expression levels from duplicate microarrays of the same animal’s RNA were correlated and averaged. Tests for differences between the before and after infection at various time points were conducted using the 2-sample Wilcoxon signed-rank test. Fold differences in the level of gene expression between after infection and before infection were calculated with the ratio of the means. After statistical analysis, data was sorted based on these transcript cutoffs: p-value of < 0.05 and fold change ≥ 2.0. Significantly changed genes and transcripts were uploaded into NetAffix Analysis Center (http://www.affymetrix.com/analysis/index.affx) to query gene ontology information and into Ingenuity Pathways Analysis (Ingenuity® Systems, www.ingenuity.com) for gene annotation and pathway analysis. Hierarchical clustering analysis was carried out by using Spotfire for DecisionSite for Functional Genomics.
2010-03-08 | GSE17626 | GEO
Project description:HIV/SIV associated oral mucosal disease/dysfunction (HAOMD) (gingivitis/periodontitis/salivary adenitis) represents a major comorbidity affecting HIV patients on anti-retroviral therapy. Using a systems biology approach, we investigated molecular changes (mRNA/microRNA) underlying HAOMD and its modulation by phytocannabinoids [delta-9-tetrahydrocannabinol (Δ9-THC)] in uninfected (n=5) and SIV-infected rhesus macaques untreated (VEH-untreated/SIV; n=7) or treated with vehicle (VEH/SIV; n=3) or Δ9-THC (THC/SIV; n=3). Relative to controls fewer mRNAs were upregulated in THC/SIV compared to VEH-untreated/SIV macaques. Gene enrichment analysis showed differential enrichment of biological functions involved in anti-viral defense, Type-I interferon, Toll-like receptor, RIG-1 and IL1R signaling in VEH-untreated/SIV macaques. We focused on the anti-ER-stress anterior gradient-2 (AGR2), epithelial barrier protecting and anti-dysbiotic WAP Four-Disulfide Core Domain 2 (WFDC2), and glucocorticoid-induced anti-inflammatory TSC22D3 (TSC22-domain family member 3) that were significantly downregulated in OPM of VEH-untreated/SIV macaques. All three proteins localized to minor salivary gland acini and secretory ducts and showed enhanced and reduced expression in OPM of THC/SIV and VEH/SIV macaques, respectively. Additionally, inflammation associated miR-21, miR-142-3p and miR-29b showed significantly higher expression in OPM of VEH-untreated/SIV macaques. TSC22D3 was validated as a target of miR-29b. These preliminary translational findings suggest that phytocannabinoids may safely and effectively reduce oral inflammatory responses in HIV/SIV and other diseases.
2020-07-01 | GSE150723 | GEO
Project description:Question Addressed: Does gene expression change in the buccal mucosa of Lymphocryptovirus (LCV) infected animals when they are chronically infected with Simian immunodeficiency virus (SIV)? Oropharyngeal mucosal tissue samples were collected from rhesus macaques. A pooled common reference was used for all hybridizations. This reference was composed of RNA harvested from rhesus macaques not infected with either LCV or SIV. Infection: Animals were infected with SIV and/or LCV
2024-05-24 | GSE38918 | GEO
Project description:In SIV/HIV infection, the gastrointestinal tissue dominates as an important site due to the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells in mediating immune activation and disease progression. We demonstrate that plasmacytoid dendritic cells (pDC) in the blood upregulate ?7-integrin and are rapidly recruited to the colorectum following a pathogenic SIV infection in rhesus macaques. These pDC were capable of producing proinflammatory cytokines and primed a Tc1 response in vitro. Consistent with the upregulation of ?7-integrin on pDC, in vivo blockade of ?4?7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The upregulation of ?7-integrin expression on pDC in the blood was also observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDC influence immune activation in colorectal tissue following pathogenic immunodeficiency virus infections. SIV negative controls (n=4) and week 12 post SIV infected (n=4) groups of Rhesus macaques and SIV negative controls (n=4) and week 55 post SIV infected (n=4) groups of Sooty mangabeys colorectal tissue biopsies were collected in to RNA later reagent (Qiagen) and were homogenized with syringe and needle method. RNA was extracted with Rneasy mini kit (Qiagen) and was used for microarray experiments. Rhesus GeneChip assays were performed in the Yerkes Microarray Core Facility (www.microarray.emory.edu) , one of the Affymetrix Microarray Core Labs.The 0.5µg of total RNA sample was analyzed on Rhesus Macaque Genome GeneChip that consists of over 52,000 probe sets (Affymetrix, Santa Clara, CA). Target RNA labeling, hybridization and post-hybridization processing were performed following the Affymetrix GeneChip Expression Analysis standard protocols. In brief, The 5 ?g of RNA sample was first reverse-transcribed using T7-Oligo(dT) Promoter Primer and SuperScript II in the first-strand cDNAs synthesis reaction. Following RNase H-mediated second-stranded cDNA synthesis, the double-stranded cDNAs were purified by use of a GeneChip sample clean-up module and served as templates in the generation of biotinylated complementary RNAs (cRNAs) in the presence of T7 RNA Polymerase and a biotinylated nucleotide analog/ribonucleotide mix by in vitro transcription (IVT) reaction. The biotinylated cRNAs were cleaned up, fragmented, and hybridized to the rhesus macaque expression arrays at 45°C for 16 h with constant rotation at 60 rpm. The gene chips were then washed and stained with Affymetrix fluidics stations 450 and scanned on Affymetrix scanner 3000. The images are processed to collect raw data with GeneChip Operating Software (GCOS) 1.4. Tissue: Colorectal tissue Time after SIV infection: 12 weeks for SIV infected Rhesus macaques, 55 weeks for Sooty mangabeys Infection: SIVmac251 infection for Rhesus macaques, SIVsm infection for Sooty mangabeys
2011-09-05 | E-GEOD-29980 | biostudies-arrayexpress
Project description:Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing.
2016-01-22 | GSE72766 | GEO
Project description:HIV cure efforts are increasingly focused on harnessing CD8 T cell functions; however, a deeper understanding of CD8 T cells promoting HIV control is necessary to properly inform therapeutic approaches. Here, we identified a novel TOX-expressing CD8 T cell population associated with control of SIV infection in lymphoid tissue of rhesus macaques defined as an antigen-responsive TCF1+ CD39+ subset expressing high levels of TOX and inhibitory receptors but lower levels of canonical cytolytic molecules such as granzyme B, granzyme A, and perforin. Transcriptional analysis of SIV-specific CD8 T cells, as well as proteomic analysis of purified CD8 T cell subsets, revealed these TCF1+ CD39+ cells as an intermediate effector population retaining stem-like features while maintaining a lineage relationship with terminal effector cells. TCF1+ CD39+ CD8 T cells expressed higher levels of CXCR5 than terminally differentiated cells, were found at higher frequency in follicular micro-environments, and were preferentially located in the proximity of SIV-RNA+ cells both in lymph node T cell zone and B cell follicles. Importantly, their frequency was strongly associated with reduced plasma viremia and lower reservoir size. Finally, we confirmed the presence of a highly similar TOX-enriched TCF1+ CD39+ cell population in lymph node biopsies from ART-naïve and ART-treated people living with HIV. Collectively, these data identify a unique population of lymphoid CD8 T cells possessing both stem-like and effector properties that contribute to limiting HIV/SIV persistence.
2024-06-11 | PXD050498 | Pride
Project description:In SIV/HIV infection, the gastrointestinal tissue dominates as an important site due to the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells in mediating immune activation and disease progression. We demonstrate that plasmacytoid dendritic cells (pDC) in the blood upregulate β7-integrin and are rapidly recruited to the colorectum following a pathogenic SIV infection in rhesus macaques. These pDC were capable of producing proinflammatory cytokines and primed a Tc1 response in vitro. Consistent with the upregulation of β7-integrin on pDC, in vivo blockade of α4β7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The upregulation of β7-integrin expression on pDC in the blood was also observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDC influence immune activation in colorectal tissue following pathogenic immunodeficiency virus infections.
2011-09-06 | GSE29980 | GEO
Project description:The objectives of this study were to determine the molecular mechanisms of host response during transition from primary to chronic SIV infection in the oral mucosa of rhesus macaques Transcriptioinal profiles were determined for 2 rhesus macaques infected for 6 wk with SIVmac251 and compared to profiles of 3 uninfected healthy controls
2009-01-12 | E-GEOD-14351 | biostudies-arrayexpress
Project description:Goal of this study was to assess the levels of protection and investigate cellular, humoral, and mucosal immune correlates on the functional and gene transcriptional levels in elite-controller macaques following high dose SIV challenge. Three experimental, post SIV smE660 challenge macaque jejunal samples were individually compared to four pre SIV smE660 challenge baseline samples.
2010-08-23 | E-GEOD-23722 | biostudies-arrayexpress