Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell transcriptional analysis of CD45+ cells in the rhesus brain during acute SIV infection.

ABSTRACT: People living with HIV are particularly vulnerable to developing a spectrum of neurocognitive abnormalities referred to as HIV-associated neurocognitive disorders. These disorders have been linked to neurological impairment driven by inflammation within areas of the brain controlling cognition. Current data suggest that HIV establishment within the central nervous system (CNS) occurs within the first weeks following infection and drives subsequent neuroinflammatory processes. Various studies have implicated HIV-target cells (i.e., monocytes, macrophages, and CD4 T cells) as key facilitators of HIV CNS establishment via a “trojan horse” mechanism, in which infected cells cross CNS barrier tissues and contribute to viral seeding. Cellular entry is mediated by integrins, specifically α4 integrins, which are expressed at the blood brain barrier and blood cerebrospinal fluid barrier and allow circulating immune cells to enter the CNS. To investigate the contribution of CNS infiltrating cells to early neurological disease, we utilized an acute rhesus macaque SIVmac251 infection model, where animals were treated with an anti-a4 integrin monoclonal antibody to inhibit immune cell trafficking to the CNS. To gain insights into neuro inflammatory transcriptional programs induced following SIV infection and how this might be modulated by a4 integrin blockade, we utilized single cell (sc) RNA sequencing of FACS sorted CD45+ cells isolated from brain and spleen.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE221815 | GEO | 2023/08/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Host response and dysfunction in the CNS during chronic simian immunodeficiency virus infection [human study]

Project description:Finding the differences in gene expression in three regions of the brai, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV inefected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients. We used microarrays to identify differentially expressed genes in normal, HIV infected, HIV inefected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients. Samples from three different brain regions from normal, HIV infected, HIV infected with neurocognitive impairment (HAD: HIV-associated dementia), and HIV infected with both neurocognitive impairment and encephalitis (HIVE: HIV encephalitis) patients were collected for RNA isolation and supsequent Affymetrix microarray analysis. We sought to obtain gene expression levels in different brain regions to find implication of HIV and the neurological impairment and inflammation associated with HIV infection.

2012-07-31 | E-GEOD-35864 | biostudies-arrayexpress

RNA-seq of select neural tissue in SHIV infected and control rhesus macaques

Project description:HIV+ patients are at an alarmingly higher risk of developing HIV associated neurocognitive disorders (HAND). HAND is a spectrum of neurocognitive deficits linked to impairments in the prefrontal cortex (PFC) and hippocampus, areas controlling higher cognitive processes. Studies in HIV+ patients implicate acute viremia and inflammation in driving central nervous system (CNS) impairment. However, the timing and implications of viral dissemination to the CNS, particularly the PFC and hippocampus, remain undefined. We tested the hypothesis that HIV-1 is rapidly and actively established within areas of the CNS responsible for controlling cognition.

2020-09-09 | GSE157690 | GEO

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

Project description:Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed microarray analysis using Affymetrix Arrays in portmortem brain tissues from seven treated and eight untreated HAND patients and six uninfected controls.

2011-09-24 | E-GEOD-28160 | biostudies-arrayexpress

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

2011-09-25 | GSE28160 | GEO

Alpha 4 integrin deficiency in human CD34+ cells engenders a precocious erythroid differentiation ,but inhibits enucleation.

Project description:The functional impact of integrin expression in erythropoiesis has been previously emphasized through its decisive influence on erythroid cell-microenvironmental (matrix and cellular) interactions especially under conditions of stress. Beyond that in several in vitro studies the relationship between the two erythroid integrins, a4 and a5, has been incongruous in terms of a proliferative support, either synergistic or antagonistic, whereas a dominant influence of a4 integrin on terminal erythropoiesis in vitro and in vivo has been consistently emphasized. However, the specific cellular and molecular details of this effect have not been defined, especially for human cells. In the present study we have cultured human CD34+ progenitor cells with induced deficiency of a4 integrin (shRNAa4) under erythroid differentiation conditions, in which expanded erythroid progenitor cells are directed to terminal erythroid maturation stages in the absence of any microenvironmental influence. Our data documented that early proliferative expansion in cells lacking a4 expression is significantly limited, but, although erythroid differentiation can proceed normally to terminal stages, their enucleation is drastically impaired. This novel aspect of a4 integrin participation in the enucleation process in vitro resonates on the lack of in vivo enucleation of primitive erythroid cells lacking any integrin expression but affecting adult cells only under stress conditions.

2022-01-17 | GSE193747 | GEO

TGF-b promotes stem-like T cells via enforcing their lymphoid tissue retention

Project description:Stem-like CD8+ T cells sustain the antigen-specific CD8+ T cell response during chronic antigen exposure. However, the signals that control the maintenance and differentiation of these cells are largely unknown. Here, we demonstrated that TGF-b was essential for the optimal maintenance of these cells and inhibited their differentiation into migratory effectors during chronic viral infection. Mechanistically, stem-like CD8+ T cells carried a unique expression pattern of a4 integrins (i.e., a4b1hi and a4b7lo) controlled by TGF-b. In the absence of TGF-b signaling, greatly enhanced expression of migration-related markers, including altered expression of a4 integrins led to enhanced egress of stem-like CD8+ T cells into the circulation accompanied by further differentiation into transitional states. Blocking a4 integrin significantly promoted their lymphoid tissue retention and therefore partially rescued the defective maintenance of Tcf-1+ subset in the absence of TGF-b signaling. Thus, TGF-b promotes the maintenance and inhibits the further differentiation of stem-like T cells at least partially via enforcing their lymphoid tissue residency.

2022-06-25 | GSE206646 | GEO

The National NeuroAIDS Tissue Consortium Brain Gene Array: Two types of HIV-associated neurocognitive impairment

Project description:Finding the differences in gene expression in three regions of the brain, basal ganglia, white matter, and frontal cortex, in normal, HIV infected, HIV infected with neurocognitive impairment, and HIV infected with both neurocognitive impairment and encephalitis patients.

2012-08-01 | GSE35864 | GEO

Immunotyping of microglia and macrophages in the CNS during acute SIV infection: a single-cell study of rhesus macaque brains

Project description:Human immunodeficiency virus (HIV) is widely recognized for its striking impact on the immune system. Even though HIV is primarily known for the impairment of the peripheral CD4 T cells, its influence on the central nervous system (CNS) also cannot be neglected. The main immune constituents in the brain, microglia and macrophages, are the target for HIV in the brain, as well as for the simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological effects as well as the establishment of a virus reservoir. Given the gaps in our knowledge on how these cells respond in vivo to CNS infection, we performed single-cell RNA sequencing (scRNA-seq) on myeloid cells from the brains of 3 rhesus macaque with 12-day SIV infection as well as 3 uninfected controls. We identified six microglial clusters and two macrophage clusters by transcriptomic profiling. Intriguingly, there were two microglial clusters populated with the cells from infected animals. These two infection-specific clusters had significantly higher expression (p < 0.05) of MHC class I molecules, interferon-induced proteins, chemokines, and cytokines than did the other clusters. Although only a low proportion of SIV-infected cells were detected in microglia and macrophages (~0.14%), almost all the microglia and macrophages in infected animals were activated to certain extents. In addition, the clusters with higher expression of cytotoxic molecules increased their populations during the infection, suggesting their potential to cause HIV-associated neurological disorders.

2024-05-01 | GSE253835 | GEO

Disrupted miRNA expression in HAND

Project description:The role of miRNA disregulation in the development of HIV associated Neurocognitive Disorder was assessed in post mortem cerebral tissue. We used microarrays to compare the expression of miRNAs in patient with HIV showing no neurological complications to those with HAND in the presence or absence of active HIV encephalitis

2017-04-11 | GSE97611 | GEO

Using Plasma Proteomics to Investigate Viral Infections of the Central Nervous System including Patients with HIV-Associated Neurocognitive Disorders

Project description:State-of-the-art liquid chromatography/mass spectrometry (LC/MS)-based proteomic technologies, using microliter amounts of patient plasma, can detect and quantify several hundred plasma proteins in a high throughput fashion, allowing for the discovery of clinically relevant protein biomarkers and insights into the underlying pathobiological processes. Using such an in-house developed high throughput plasma proteomics allowed us to identify and quantify > 400 plasmas proteins in 15 minutes per samples, i.e., a throughput of 100 samples/day. We demonstrated the clinical applicability of our method in this pilot study by mapping the plasma proteomes from patients infected with human immunodeficiency virus (HIV) or herpes virus, both groups with involvement of the central nervous system (CNS). We found significant disease-specific differences in the plasma proteomes. The most notable difference was a decrease in the levels of several coagulation-associated proteins in HIV vs. herpes virus, amongst other dysregulated biological pathways providing insight into the differential pathophysiology of HIV compared to herpes virus infection. In a subsequent analysis, we found several plasma proteins associated with immunity and metabolism to differentiate patients with HIV-associated neurocognitive disorders (HAND) compared to cognitively normal people with HIV (PWH), suggesting the presence of plasma-based biomarkers to distinguishing HAND from cognitively normal PWH. Overall, our high-throughput plasma proteomics pipeline enables identification of distinct proteomic signatures of HIV and herpes virus, which may help illuminate divergent pathophysiology behind virus-associated neurological disorders.

2024-03-05 | PXD047528 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data