Expression data from human monocyte derived dendritic cells infected with adenovirus expressing HIV-1 Vpr
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE61171 | GEO | 2014/09/06
SECONDARY ACCESSION(S): PRJNA260396
REPOSITORIES: GEO
Similar Datasets
Project description:HIV-1 Vpr protein is a multifunctional protein which perturbs human transcriptome and interacts with a number of cellular proteins. In this study, we have attempted to explore the efffects of Vpr on human transcriptome and have identified several genes which are involved in innate immune responses. We used the microarray analysis to elucidate the differnetail expression pattern of differnet genes in human dendritic cells infected with HIV-1 Vpr. As result we found that HIV-1 Vpr protein leads to the induction of various interferon stimualted genes (ISGs) in human monocyte derived dendritic cells. Human monocytes-derived dendritic cells (MDDCs) were isolated from peripheral blood mononuclear cells (PBMCs) from two healthy donors and were infected with recombinant adenoviruses either expressing HIV-1 Vpr or ZsGreen1 as a control. At 48 hours post-infection, RNA was isolated and subjected to microarray analysis.
2014-09-06 | E-GEOD-61171 | biostudies-arrayexpress
Project description:HIV-1 Vpr protein is a multifunctional protein which perturbs human transcriptome and interacts with a number of cellular proteins. In this study, we have attempted to explore the efffects of Vpr on human transcriptome and have identified several genes which are involved in innate immune respone and cell signaling pathways. We used the microarray analysis to elucidate the differnetail expression pattern of differnet genes in human macrophages infected with HIV-1 Vpr. As result we found that HIV-1 Vpr protein leads to the induction of various interferon stimualted genes (ISGs) and chemokines in human macrophages.
2014-04-09 | GSE56591 | GEO
Project description:HIV-1 Vpr protein is a multifunctional protein which perturbs human transcriptome and interacts with a number of cellular proteins. In this study, we have attempted to explore the efffects of Vpr on human transcriptome and have identified several genes which are involved in innate immune respone and cell signaling pathways. We used the microarray analysis to elucidate the differnetail expression pattern of differnet genes in human macrophages infected with HIV-1 Vpr. As result we found that HIV-1 Vpr protein leads to the induction of various interferon stimualted genes (ISGs) and chemokines in human macrophages. Human monocytes-derived macrophages (MDMs) were isolated from peripheral blood mononuclear cells (PBMCs) from two healthy donors and were infected with recombinant adenoviruses either expressing HIV-1 Vpr or ZsGreen1 as a control. At 48 hours post-infection, RNA was isolated and subjected to microarray analysis.
2014-04-09 | E-GEOD-56591 | biostudies-arrayexpress
Project description:Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders. Human fetal neurons were chosen to examine the impact of HIV-1 Vpr protein on gene expression
2012-12-07 | E-GEOD-42424 | biostudies-arrayexpress
Project description:Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders. Using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Vpr) on the expression of miRNAs and mRNAs.
2013-02-12 | E-GEOD-44266 | biostudies-arrayexpress
Project description:Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders. Human neurons SH-SY5Y were chosen to examine the impact of HIV-1 Vpr protein on gene expression
2013-01-17 | E-GEOD-43535 | biostudies-arrayexpress
Project description:HIV-1 accessory protein, Vpr, is required for efficient HIV-1 infection of macrophages. Here we show that Vpr reprograms macrophage gene expression by altering the activity of master transcriptional regulator, PU.1, which is responsible for regulating the expression of host immune response genes and is necessary for normal hematopoiesis. In HIV-infected primary macrophages, Vpr-dependent changes in PU.1 levels result in suppression of known anti-viral targets of Vpr including IFITM3 and MRC1. Moreover, we find that PU.1 and its co-factor TET2 are co-recruited to DCAF1 by Vpr and targeted for accelerated degradation. Downmodulation of PU.1 is a highly conserved function of Vpr that is maintained across primate lentiviruses including HIV-2 and several SIVs. In contrast, this activity is not shared by the evolutionarily related accessory protein Vpx. Our findings demonstrate how Vpr dramatically enhances HIV spread in macrophages by targeting a myeloid-specific transcription factor needed for expression of multiple viral restriction factors.
2024-04-30 | GSE220574 | GEO
Project description:Studies have shown that HIV-infected patients develop neurocognitive disorders characterized by neuronal dysfunction. The lack of productive infection of neurons by HIV suggests that viral and cellular proteins, with neurotoxic activities, released from HIV-1-infected target cells can cause this neuronal deregulation. The viral protein R (Vpr), a protein encoded by HIV-1, has been shown to alter the expression of various important cytokines and inflammatory proteins in infected and uninfected cells; however the mechanisms involved remain unclear. Using a human neuronal cell line, we found that Vpr can be taken up by neurons causing: (i) deregulation of calcium homeostasis, (ii) endoplasmic reticulum-calcium release, (iii) activation of the oxidative stress pathway, (iv) mitochondrial dysfunction and v- synaptic retraction. In search for the cellular factors involved, we performed microRNAs and gene array assays using human neurons (primary cultures or cell line, SH-SY5Y) that we treated with recombinant Vpr proteins. Interestingly, Vpr deregulates the levels of several microRNAs (e.g. miR-34a) and their target genes (e.g. CREB), which could lead to neuronal dysfunctions. Therefore, we conclude that Vpr plays a major role in neuronal dysfunction through deregulating microRNAs and their target genes, a phenomenon that could lead to the development of neurocognitive disorders.
2013-02-12 | GSE44266 | GEO
Project description:Viruses target host proteins for degradation to enhance their replication and transmission, and identifying these targets has provided key insights into the host-pathogen interaction1-3. Here, we use complementary unbiased mass spectrometry-based approaches to dissect the widespread proteomeic remodelling seen in HIV-1 infected T-cells. Remarkably, the HIV accessory protein Vpr is both necessary and sufficient to cause the vast majority of these changes. Protein regulation requires recruitment of the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex, and pulsed-Stable Isotope Labelling with Amino Acids in Cell Culture (SILAC) and immunoprecipitation-mass spectrometry (IP-MS) identified at least 38 cellular proteins directly targeted for degradation by Vpr. Whilst other HIV-1 accessory proteins downregulate a small number of specific host factors, Vpr depletes multiple protein targets, causing systems-level changes to the cellular proteome. A subset of the novel cellular targets identified in this study are depleted by Vpr variants from across HIV-1/SIVcpz and other primate lentiviral lineages, confirming their biological importance in vivo.
2019-05-01 | PXD013221 | Pride
Project description:Lentiviral accessory genes enhance replication through diverse mechanisms. HIV-1 accessory protein Vpr modulates the host DNA damage response (DDR) at multiple steps through DNA damage, cell cycle arrest, the degradation of host proteins, and both the activation and repression of DDR signaling. Vpr also alters host and viral transcription; however, the connection between Vpr-mediated DDR modulation and transcriptional activation remains unclear. Here, we determined the cellular consequences of Vpr-induced DNA damage using Vpr mutants that allow us to separate the ability of Vpr to induce DNA damage from cell cycle arrest and other DDR phenotypes including host protein degradation and repression of DDR. RNA-sequencing of cells expressing Vpr or Vpr mutants identified that Vpr alters cellular transcription through mechanisms both dependent and independent of cell cycle arrest. In tissue-cultured U2OS cells and primary human monocyte-derived macrophages (MDMs), Vpr-induced DNA damage activates the ATM-NEMO pathway and alters cellular transcription via NF-κB/RelA signaling. HIV-1 infection of primary MDMs validated Vpr-dependent NF-κB transcriptional activation during infection. Both virion delivered and de novo expressed Vpr induced DNA damage and activated ATM-NEMO dependent NF-κB transcription, suggesting that engagement of the DDR and transcriptional reprogramming can occur during early and late stages of viral replication. Together, our data identifies a mechanism by which Vpr activates NF-κB through DNA damage and the ATM-NEMO pathway, which occur independent of cell cycle arrest. We propose this is essential to overcoming restrictive environments, such as in macrophages, to enhance viral transcription and replication.
2024-08-23 | GSE253779 | GEO