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Expression data of human CD4 T cells with chronic or acute simian immunodeficiency virus (SIV) infection

ABSTRACT: We compared gene expression profiles of a human CD4+ T-cell line 24 h after infection with a cell line of the same origin permanently releasing SIVmac251/32H. A new knowledge-based-network approach (Inter-Chain-Finder) was used to identify subnetworks leading to resistance to SIV-induced cell death. Notably, the method can identify not only differentially-expressed key hub genes but also non-differentially expressed, critical, ‘hidden’ regulators. 6 out of the 13 predicted major hidden key regulators were among the landscape of proteins known to interact with HIV. Several subnetworks were dysregulated upon chronic infection with SIV. Most prominently, factors engaged in early stages of viral infection were affected, e.g. entry, integration and provirus transcription or cellular responses like apoptosis and proliferation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE51594 | GEO | 2014/08/27

SECONDARY ACCESSION(S): PRJNA223669

REPOSITORIES: GEO

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Expression data of human CD4 T cells with chronic or acute simian immunodeficiency virus (SIV) infection

Project description:We compared gene expression profiles of a human CD4+ T-cell line 24 h after infection with a cell line of the same origin permanently releasing SIVmac251/32H. A new knowledge-based-network approach (Inter-Chain-Finder) was used to identify subnetworks leading to resistance to SIV-induced cell death. Notably, the method can identify not only differentially-expressed key hub genes but also non-differentially expressed, critical, ‘hidden’ regulators. 6 out of the 13 predicted major hidden key regulators were among the landscape of proteins known to interact with HIV. Several subnetworks were dysregulated upon chronic infection with SIV. Most prominently, factors engaged in early stages of viral infection were affected, e.g. entry, integration and provirus transcription or cellular responses like apoptosis and proliferation. Human CD4 T cells with different types of SIV infection were used for RNA extraction and hybridization on Affymetrix HG_U133A microarrays. Our aim is to identify subnetworks in T cells leading to resistance to SIV-induced cell death. To the end, we compared acute infection with chronic infection and mock control infection. Each pair (including three types of infection) was done in duplicate.

2014-08-27 | E-GEOD-51594 | biostudies-arrayexpress

Deep transcriptional sequencing of mucosal challenge compartment from rhesus macaques acutely infected with simian immunodeficiency virus implicates loss of cell adhesion preceding immune activation

Project description:Recent studies of nonhuman primates (NHPs) have suggested that during the acute phase of infection, antiviral mucosal immunity is restricting viral replication in the primary infection compartment. These studies imply that HIV achieves systemic infection as a consequence of a failure in host antiviral immunity. Here, we used high-dose intrarectal inoculation of rhesus macaques with SIVmac251 to examine how the mucosal immune system is overcome by SIV during acute infection. The host response in rectal mucosa was characterized by mRNA deep sequencing (mRNA-seq) at 3 and 12 days post inoculation (DPI) in 4 animals for each time point. The eight RMs were intrarectally challenged with SIVmac251 using 1 mL of a high-dose inoculum (6000 TCID50/mL). SIV inoculates were deposited at a rectal depth of 25 mm from the anus. Baseline rectal samples were obtained 14 days prior to viral challenge by pinch biopsy.

2014-04-17 | E-GEOD-56845 | biostudies-arrayexpress

Innate protection against intrarectal SIV acquisition by a live Simian-Human immunodeficiency virus vaccine

Project description:Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical against SIV/HIV acquisition. Here, we evaluated the efficacy of a SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded as there was no cross-reactivity between SIV and SHIV Envelope antibodies. After eight low-dose rectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated 83% efficacy, compared to six naïve controls, suggesting protection could be achieved in the absence of anti-Envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for the preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation, and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 (PF4) on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity and may provide new opportunities for novel HIV vaccines or therapeutic strategy development.

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Deep transcriptional sequencing of mucosal challenge compartment from rhesus macaques acutely infected with simian immunodeficiency virus implicates loss of cell adhesion preceding immune activation

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Host response and dysfunction in the CNS during chronic simian immunodeficiency virus infection

Project description:Molecular basis for CNS dysfunction in simian immunodeficiency virus-infected rhesus monkeys. We used microarrays to identify differentially expressed genes in chronic simian immunodeficiency virus-infected rhesus monkeys. Frontal lobe samples were obtained from control and SIV infected animals for RNA extraction and hybridization on Affymetrix microarrays. We sought to better understand the gene that changes in gene expression with SIV infection in the frontal lobe.

2012-01-29 | E-GEOD-35397 | biostudies-arrayexpress

Simian immunodeficiency virus strain:SIVmac251

Project description:SIVmac251 in vaccinated and naive cynomolgus macaques.

| PRJNA528275 | ENA

Innate protection against intrarectal SIV acquisition by a live Simian HIV vaccine

Project description:Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical against SIV/HIV acquisition. Here, we evaluated the efficacy of a SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded as there was no cross-reactivity between SIV and SHIV Envelope antibodies. After eight low-dose rectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated 83% efficacy, compared to six naïve controls, suggesting protection could be achieved in the absence of anti-Envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for the preventing viral acquisition, as none of the CD8-depleted macaques was infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation, and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 (PF4) on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity and may provide new opportunities for novel HIV vaccines or therapeutic strategy development.

2024-08-30 | GSE241963 | GEO

Simian immunodeficiency virus strain:SIVmac251

Project description:Simian immunodeficiency virus strain:SIVmac251 Raw sequence reads

| PRJNA551921 | ENA

CD32+CD4+ T cells sharing B cell properties increase in lymphoid tissues during simian immunodeficiency virus infection

Project description:HIV reservoirs in tissues form the major hurdle to an HIV cure. Despite major progress made on the understanding of the establishment and persistence of viral reservoirs, the characterization of composition and dynamics of the viral reservoir is still uncomplete. In addition, most studies in HIV infection are limited to blood. Here we take advantage of non-human primate models to provide a longitudinal analysis on potential viral target cells in distinct body compartments : blood, lymph nodes (LN), spleen ileum, jejunum and liver. We observed an increase in CD32+CD4+ T cells in secondary lymphoid tissues and intestine during primary and chronic pathogenic SIVmac infection. In the natural host (African green monkey, AGM), increase of the CD4+CD32+T cell levels was observed in tissues with higher replication and immune activation. CD32+CD4+ T cells expressed more often markers associated with HIV infected and/or reservoir cells (PD-1, CXCR5 for TFH cells in SLT, and CXCR3 for Th1 cells) than CD32- cells. The tissue CD32+CD4+T cells displayed higher levels of actively transcribed SIV RNA than CD32-CD4+T cells. The genome-wide transcriptome of CD32+CD4+ T cells in spleen from SIV-infected animals indicated that the CD32+CD4+ T cells shared B cell markers. The CD20+ expressing CD32+CD4+ T cells were increased in the tissues but not in the blood during SIV infection. Altogether, the study showed that SIV infection increases the frequencies of CD32+CD4+ T cells in tissues more than in blood. These cells might represent a not well-described subpopulation of activated CD4+ T cells.

2021-04-16 | GSE169736 | GEO

Chronic Binge Alcohol Administration Dysregulates Expression of Hippocampal Genes Involved in Immune Function, Neurotransmission and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

Project description:HIV-associated neurocognitive disorder is prevalent despite wide-spread use of effective anti-retroviral therapy (ART). Alcohol use disorders (AUDs) exacerbate neurocognitive dysfunction in HIV+ patients. Previously we have shown that chronic binge alcohol administration (CBA, 13 – 14 g EtOH/kg/wk) starting 3 months prior to simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks behavioral deficits. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. The aim of this study was to explore the alterations in hippocampal gene expression of CBA administered, SIV-infected (CBA/SIV+; N=2) macaques and isocaloric sucrose administered, SIV-infected (SUC/SIV+; N=2) macaques in contrast to uninfected (SIV-; N=2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation) were analyzed using Illumina Custom algorithm to determine differentially expressed genes (p-value filter of ≤ 0.05; either ≥ 1.3 fold change or ≤ 0.76 fold change) between SUC/SIV+ and SIV-, CBA/SIV+ and SIV-, and CBA/SIV+ and SUC/SIV+. We used Gene Codis to determine enrichment of specific Gene Ontology Biological Processes from both the SUC/SIV+ and CBA/SIV+ gene lists. Gene Codis analysis revealed over-representation of genes involved in neurodevelopment, neurotransmission, interferon-signaling, and antigen presentation in the CBA/SIV+ group. Further analysis of differentially expressed genes between SIV- and CBA/SIV+ showed predominantly up-regulation of immune function genes and down-regulation of nervous system development and synaptic transmission genes in CBA/SIV+ animals. These findings provide insight into the potential mechanisms by which CBA may enhance neurobehavioral deficits.

2016-12-12 | GSE69685 | GEO

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