The major inducible 70 kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. Focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and non-transgenic (NT) mice 5 days after infection identified type 1 interferon (IFN) signaling and macrophage activation/antigen presentation as the main differences linked to survival. The pivotal role for type 1 IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type 1 IFN receptor (IFNAR-/-), where IFNAR-/- eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type 1 IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN- in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN- transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, results support a novel axis of type 1 IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.
hsp70 and a novel axis of type I interferon-dependent antiviral immunity in the measles virus-infected brain.
Age, Specimen part, Treatment
View SamplesUntreated HIV-1 infection progresses through acute and asymptomatic stages to AIDS. While each of the three stages has well-known clinical, virologic and immunological characteristics, much less is known of the molecular mechanisms underlying each stage. Here we report lymphatic tissue microarray analyses revealing for the first time stage-specific patterns of gene expression during HIV-1 infection. We show that while there is a common set of key genes with altered expression throughout all stages, each stage has a unique gene-expression signature. The acute stage is most notably characterized by increased expression of hundreds of genes involved in immune activation, innate immune defenses (e.g.MDA-5, TLR-7 and -8, PKR, APOBEC3B, 3F, 3G), adaptive immunity, and in the pro-apoptotic Fas-Fas-L pathway. Yet, quite strikingly, the expression of nearly all acute-stage genes return to baseline levels in the asymptomatic stage, accompanying partial control of infection. In the AIDS stage, decreased expression of numerous genes involved in T cell signaling identifies genes contributing to T cell dysfunction. These common and stage-specific, gene-expression signatures provide new insights into the molecular mechanisms underlying the host response and the slow, natural course of HIV-1 infection.
Microarray analysis of lymphatic tissue reveals stage-specific, gene expression signatures in HIV-1 infection.
Sex, Age, Specimen part, Disease, Disease stage, Race, Subject
View Samples10 day old seedlings were treated with 5uM of the cytokinin Benzyladenine(BA)or DMSO at 15min, 45min, 120min, 480min and 1440min
Expression profiling of cytokinin action in Arabidopsis.
Age, Compound, Time
View SamplesSystemic vaccination with the attenuated virus SIVmac239-Nef provides sterilizing or partial protection to rhesus monkeys challenged with WT SIV strains, providing important opportunities to study key immunological components of a protective host response. Here we show that intravenous vaccination with SIVmac239-Nef provides two potentially crucial immunological barriers localized at mucosal surfaces that correlate with the vaccines protective effects against WT SIVmac251 vaginal challenge: 1) a conditioned and coordinated response from the mucosal epithelium that blunts the early inflammatory and chemotactic signalling cascade that aids virus propagation and expansion; 2) early on-site generation/diversification of SIV-specific Abs from ectopic germinal center-like lymphoid aggregates. This unique host response to WT SIVmac251 in the female reproductive tract of SIVmac239-Nef-vaccinated animals points to a multi-layered strategy for a protective host response during immunodeficiency virus exposurerapid induction of humroal immunity at mucosal surfaces without the deleterious inflammatory side effects tied to innate recognition of virus. This vaccine-induced host response highlights potential key protective mechanisms needed for an effective HIV vaccine
Live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability.
Sex, Specimen part
View SamplesInflorescence stages 1 to 12 from mutants involved in Arabidopsis small RNA metabolism. Three biological replicates of each mutant comprising at least 9 independent plants were harvested, and the expression profiles were determined using Affymetrix ATH1 arrays. Comparisons among the sample groups allow the identification of genes regulated by small RNAs (microRNAs and siRNAs).
microRNA-directed phasing during trans-acting siRNA biogenesis in plants.
No sample metadata fields
View SamplesClinicians need additional metrics for predicting quality of human oocytes for IVF procedures. Human polar bodies reflect the oocyte transcript profile. Quantitation of polar body mRNAs could allow for both oocyte ranking and embryo preferences in IVF applications. The transcriptome of a polar body has never been reported, in any organism. Overall design: Eight total samples. There are 2 biological replicates of the following four conditions: pooled oocytes and their sister polar bodies and a single oocyte and its sister polar body.
The transcriptome of a human polar body accurately reflects its sibling oocyte.
Specimen part, Subject
View SamplesEpithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are recently discovered epithelial-specific RNA-binding proteins that promote splicing of the epithelial variant of the FGFR2, ENAH, CD44, and CTNND1 transcripts. To catalogue a larger set of splicing events under the regulation of the ESRPs, we profiled splicing changes induced by RNA interference-mediated knockdown of ESRP1 and ESRP2 expression in a human epithelial cell line using the splicing-sensitive Affymetrix Exon ST1.0 Arrays. Analysis of the microarray data using the previously described MADS tool resulted in the identification of over a hundred candidate ESRP-regulated splicing events. We were able to independently validate 37 of these targets by RT-PCR. The ESRP-regulated events encompass all known types of alternative splicing events. Importantly, a number of these regulated splicing events occur in gene transcripts that encode proteins with well-described roles in the regulation of actin cytoskeleton organization, cell-cell adhesion, cell polarity, and cell migration. In sum, this work reveals a novel list of transcripts differentially spliced in epithelial and mesenchymal cells, implying that coordinated alternative splicing plays a critical role in determination of cell type identity.
The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate diverse types of alternative splicing events.
Specimen part, Cell line
View SamplesMM1.S cells stably transduced with control or b-catenin shRNA were established. Total RNA was isolated from 5x 10^6 cells of each in triplicate.
Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression.
Cell line
View SamplesComparison of sense (forward probes) and antisense (reverse probes on U74 v1 gene arrays) transcripts in mouse kidney and brain.
Expression profiling of antisense transcripts on DNA arrays.
No sample metadata fields
View SamplesTHREE INDEPENDENT REPLICATES AND ARE THE CONTROL NON-INFECTED CELLS:
Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum.
No sample metadata fields
View Samples