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GSE12254
Macaca mulatta
19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rhesus macaques (Macaca mulatta) infected with a lethal dose of lymphocytic choriomeningitis virus-strain WE (LCMV-WE) provide a model for Lassa fever virus infection of man. Like Lassa fever in human beings, disease begins with flu-like symptoms but can progress to morbidity fairly rapidly. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al. J. Virol. 2007: PMID 17522210) showing distinct pre-viremic and viremic stages that discriminated between virulent and benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased. We observed gene expression changes that occurred before the viremic stage of the disease, and could potentially serve as biomarkers that discriminate between exposure to a hemorrhagic fever virus and exposure to a benign virus. Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a much broader effect on liver cell function than non-virulent virus. During the first few days of infection, virulent virus impacted gene expression associated with the generation of energy, such as fatty acid metabolism and glucose metabolism, with the complement and coagulation cascades, and with steroid metabolism, MAPK signaling and cell adhesion. For example, the energy profile resembled that of an organism entering starvation: acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis, was shut down and gene products involved in gluconeogenesis were up-regulated. In conclusion, this study identifies several potential gene markers of LCMV-WE-associated liver disease and contributes to the database of gene expression changes correlated with LCMV pathogenesis in primates.
Publication Title
Gene expression in primate liver during viral hemorrhagic fever.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Type I interferons were discovered as the primary antiviral cytokines and are now known to serve critical functions in host defense against bacterial pathogens. Accordingly, established mediators of interferon antiviral activity may mediate previously unrecognized antibacterial functions. RNase-L is the terminal component of an RNA decay pathway that is an important mediator of interferon-induced antiviral activity. Here we identify a novel role for RNase-L in the host antibacterial response. RNase-L-/- mice exhibited a dramatic increase in mortality following
Publication Title
An essential role for the antiviral endoribonuclease, RNase-L, in antibacterial immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The virulent Lassa fever virus (LASV) and the non-pathogenic Mopeia virus (MOPV) infect rodents and incidentally people in West Africa. The mechanism of LASV damage in human beings is unclear. A live-attenuated reassortant of MOPV and LASV protects rodents and primates from Lassa fever disease. Peripheral blood mononuclear cells from healthy human subjects were expose to either LASV or ML29 in order to identify early cellular responses that could be attributed to the difference in virulence between both viruses. Differential expression of interferon-related genes as well as coagulation-related genes could lead to an explanation for Lassa fever pathogenesis and lead to protective treatments for Lassa fever disease.
Publication Title
Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29), a vaccine candidate.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lassa fever virus is a zoonotic pathogen that plagues the endemic areas of West Africa. Rhesus macaques infected with a related arenavirus, LCMV-WE, serve as a model for Lassa-infection of human beings. Using a dose similar to that expected from a needle-stick, monkeys experience an early pre-viremic phase (day 1-3), a viremic phase with febrile onset (day 4-7), and, like human beings who succumb, they die within two weeks. Our goal was to monitor changes in gene expression that parallel disease progression in an effort to 1) identify genes with altered expression after infection, 2) identify genes that could discriminate between a virulent and non-virulent infection, and 3) identify genes encoding products that could serve as treatment targets for FDA-approved pharmaceuticals. Genes related to all three of these categories have been identified and some have been given preliminary validation by quantitative PCR and proteomic studies. These genes will be valuable candidates for future validation as prognostic biomarkers
Publication Title
Early blood profiles of virus infection in a monkey model for Lassa fever.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lassa fever (LF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs of virulent disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of AIDS. SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, weight loss, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections included increased expression of interferon response genes and decreased expression of COX2, IL-1?, coagulation intermediates and nuclear receptors needed for stress signaling. Here it is demonstrated that SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and that none developed signs of arenavirus disease or persistence. Furthermore, 5 of 5 animals given a heterologous challenge with a lethal dose of LCMV-WE survived without developing disease signs.
Publication Title
An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Human transcriptome analysis of U2OS cells treated with nocodazole or DMSO (Control).
Publication Title
Autophagy Governs Protumorigenic Effects of Mitotic Slippage-induced Senescence.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
IlluminaHiSeq2000
Description
T follicular helper (Tfh) cells are a subset of CD4+ T helper (Th) cells that migrate into germinal centers and promote B cell maturation into memory B and plasma cells. Tfh cells are necessary for promotion of protective humoral immunity following pathogen challenge, but when aberrantly regulated, drive pathogenic antibody formation in autoimmunity and undergo neoplastic transformation in angioimmunoblastic T-cell lymphoma and other primary cutaneous T-cell lymphomas. Limited information is available on the expression and regulation of genes in human Tfh cells. Using a fluorescence activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector (Teff) cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by ChIP-seq, with parallel transcriptome analyses determined by RNA-seq. Tfh cell enhancers were enriched near genes highly expressed in lymphoid cells or involved in lymphoid cell function, with many mapping to sites previously associated with autoimmune disease in genome-wide association studies. A group of active enhancers unique to Tfh cells associated with differentially expressed genes was identified. Fragments from these regions directed expression in reporter gene assays. These data provide a significant resource for studies of T lymphocyte development and differentiation and normal and perturbed Tfh cell function. Overall design: Using a fluorescence activated cell sorting-based strategy, we obtained primary Tfh and non-Tfh T effector (Teff) cells from tonsils and prepared genome-wide maps of active, intermediate, and poised enhancers determined by ChIP-seq, with parallel transcriptome analyses determined by RNA-seq.
Publication Title
Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Investigating neuronal and photoreceptor regeneration in the retina of zebrafish has begun to yield insights into both the cellular and molecular means by which this lower vertebrate is able to repair its central nervous system. However, knowledge about the signaling molecules in the local microenvironment of a retinal injury and the transcriptional events they activate during neuronal death and regeneration is still lacking. To identify genes involved in photoreceptor regeneration, we combined light-induced photoreceptor lesions, laser-capture microdissection (LCM) of the outer nuclear layer (ONL) and analysis of gene expression to characterize transcriptional changes for cells in the ONL as photoreceptors die and are regenerated. Using this approach, we were able to characterize aspects of the molecular signature of injured and dying photoreceptors, cone photoreceptor progenitors and microglia within the ONL. We validated changes in gene expression and characterized the cellular expression for three novel, extracellular signaling molecules that we hypothesize are involved in regulating regenerative events in the retina.
Publication Title
Identification of the molecular signatures integral to regenerating photoreceptors in the retina of the zebra fish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inadequate protein intake initiates an accommodative response with adverse changes in skeletal muscle function and structure. mRNA level changes due to short-term inadequate dietary protein might be an early indicator of accommodation. The aims of this study were to assess the effects of dietary protein and the diet-by-age interaction on the skeletal muscle transcript profile. Self-organizing maps were used to determine expression patterns across protein trials.
Publication Title
The skeletal muscle transcript profile reflects accommodative responses to inadequate protein intake in younger and older males.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 42 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The origins of breast cancer prognostic gene expression profiles.
Sample Metadata Fields
No sample metadata fields
View Samples