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GSE79417
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
West Nile virus (WNV) is the most important cause of endemic encephalitis in the USA. Strikingly, only a small percentage of patients develop clinical disease and of these patients, approximately 1 out of 150 patients develops encephalitis. The basis for this great variability in disease outcome is unknown, but may be related to the innate immune response. Innate immune responses, critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors (PRR) such as RIG-I and MDA5. IPS-1 is a key adaptor in generating a PRR-dependent interferon response.. Here we show that IPS-1 deficiency in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In IPS-1-/- mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were multifunctional and were able to lyse peptide-pulsed target cells in vitro. However, virus-specific T cells in the infected IPS-1-/- brain exhibited lower functional avidity than those in C57BL/6 brains, possibly contributing to less efficient virus clearance. The presence of virus-specific memory T cells was also not protective. We also show that macrophages were increased in numbers in the IPS-1-/- brain. Both macrophages and microglia exhibited an activated phenotype. Microarray analyses showed the preferential upregulation of genes associated with leukocyte activation and inflammation. Together, these results demonstrate the critical role that hematopoietic cell expression of Type 1 interferon and other IPS-1-dependent molecules have in WNV clearance and in regulating the inflammatory response.
Publication Title
MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Type I interferon-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20 kDa ISG, ISG20, is a nuclear 3''-5''exonuclease with preference for single stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20-/- mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20-/- mice compared to wild-type viruses, but not in ISG20 ectopic-expressing cells. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expressionof other ISGs that inhibit translation and possibly other activities in the replication cycle. Overall design: Two clones each of tet-inducible MEFs overexpressing eGFP (control), Isg20, and Isg20(D94G) were induced by tetracycline removal for 72 hours. rRNA was depleted with RiboMinus Eukaryote kit (Life Technologies) and prepared for Illumina directional 100bp paired-end HiSeq2000 reads.
Publication Title
The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina Genome Analyzer II
Description
We report on abundance and transcript profile characteristics of sperm RNAs. Overall design: Examination of RNA population and distribution in spermatozoa
Publication Title
Stability, delivery and functions of human sperm RNAs at fertilization.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor (TGF) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGF hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in a pre-clinical model of metastatic breast cancer.
Publication Title
TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 72 Downloadable Samples
- IlluminaHiSeq2500
Description
We examine how NGS sequencing of sperm can provide a window as to how particular perturbations of the sperm RNA profile from baseline may be indicative of male factor infertility, and may thus provide direction as to proper course of infertility treatment for couple. Overall design: NGS RNA-seq of 72 sperm samples from male partner of couples undergoing fertility treatment
Publication Title
Absence of sperm RNA elements correlates with idiopathic male infertility.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Although type III interferons (IFN), also known as IFN-? or IL28/IL-29, restrict infection by several viruses, their mechanism of inhibitory action has remained uncertain. We used recombinant IFN-? and mice lacking the IFN-? receptor (IFNLR1) to evaluate the effect of IFN-? on infection with West Nile virus (WNV), an encephalitic flavivirus. Cell culture studies in keratinocytes and dendritic cells showed no direct antiviral effect of exogenous IFN-? even though ISGs were induced. Correspondingly, we observed no differences in WNV burden between wild-type and Ifnlr1-/- mice in the draining lymph node, spleen, and blood. However, we detected earlier dissemination and increased WNV infection in the brain and spinal cord of Ifnlr1-/- mice, yet this was not associated with a direct antiviral effect on infection of neurons. Instead, an increase in blood-brain barrier (BBB) permeability was observed in Ifnlr1-/- mice. Accordingly, treatment of mice with pegylated IFN-?2 resulted in decreased BBB permeability, reduced WNV infection in the brain without impacting viremia, and improved survival against lethal virus challenge. An in vitro model of the BBB showed that IFN-? signaling in brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and STAT1-independent manner. Our data establish a novel indirect antiviral function of IFN-? in which non-canonical signaling through IFNLR1 tightens the BBB and restricts viral neuroinvasion and pathogenesis. This finding suggests new clinical applications for IFN-? in treating viral or autoimmune diseases. Overall design: Transcriptome profiling of bone-marrow derived Dendritic cells(BMDCs), treated with either Serum Free Media(Mock), interferon beta(IFNb), or interferon lambda(IFNL) for 6 hours.
Publication Title
Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Normal human spermatogenesis concludes with the formation of large numbers of morphologically well developed spermatozoa. While transcriptionally quiescent these cells carry an RNA payload that reflects the final spermiogenic phase of transcription. We report here the spermatozoal transcript profiles characteristic of normally fertile individuals and infertile males suffering from a consistent and severe teratozoospermia in which under 4% of spermatozoa are morphologically normal. RNA was extracted from the purified sperm cells of ejaculate and hybridized to Affymetrix U133 (v2) Microarrays.
Publication Title
Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression of Tfap4/ and WT CD8+ T cells were compared after activation with anti-CD3 and anti-CD28 antibodies in vitro or with Listeria monocytogenes infection in vivo
Publication Title
c-Myc-induced transcription factor AP4 is required for host protection mediated by CD8+ T cells.
Sample Metadata Fields
No sample metadata fields
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