Tick-borne flaviviruses (TBFVs) are ss(+)RNA viruses that cause febrile illnesses, which may progress to severe encephalitis and/or death in humans globally. 30—60% of people who recover from severe acute disease continue to suffer debilitating neurological sequelae due to viral persistence, neurological cell damage incurred during infection and/or host response, or a combination of these. When TBFVs infect mammalian cells in vitro, an acute phase characterized by dramatic apoptosis ensues and kills >95% of infected cells by day 5. Upon refreshing the cell growth medium, surviving cells repopulate and become persistently infected for extended periods of time. However, molecular mechanisms responsible for the initiation and maintenance of viral persistence in vivo and in vitro remain vague. We used unbiased deep sequencing of the HEK 293T cell transcriptome to determine the profiles of acutely infected cells at selected time points as well as of persistently infected cells. Many genes were significantly differentially expressed during the course of the acute phase, but 451 genes were significantly differentially expressed uniquely in persistently infected cells. Ingenuity Pathways Analysis of these genes suggested that the oncogenes AKT2 and ERBB2, which favor cell survival were up-regulated in persistently infected cells, whereas pro-apoptotic genes, such as Bad and IFN-ß1 were down-regulated. There was also an up-regulation of genes encoding antiviral cytokines, such as CCL5, TNF-a and CXCL10 during the acute phase, but these were relatively suppressed in persistently infected cells. Exogenous induction of apoptosis in persistently infected cells with chelerythrine chloride indicated that these cells were resistant to apoptosis in a dose-dependent manner. In summary, the transcriptome profiles of acutely and persistently infected HEK 293T cells are different and evasion of apoptosis is critical for the initiation of TBFV persistence. These results provide a basis for further studying the precise molecular mechanisms of TBFV persistence.
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View SamplesWe undertook a survey of gene expression changes in primary microglial cultures with and without neurovirulent (FrCasE) and non-neurovirulent (Fr57E) virus infection to identify physiological changes that could be relevant to the induction of spongiform neurodegeneration. These gene expression analyses were performed using Affymetrix 430A mouse GeneChips (5 chips for each of the three experimental conditions, representing over 14,000 murine genes and ESTs. RNA from 5 separate microglial culture preparations were analyzed for Control (mock infected), Fr57E-, and FrCasE-infected microglia. Present/absent calls were based on MicroArray Suite 5.0 from Affymetrix. Affymetrix CEL files were analyzed using dChip software after normalization of the data between all 15 arrays. Statistical analyses were performed using ANOVA.
Gene expression profiling of microglia infected by a highly neurovirulent murine leukemia virus: implications for neuropathogenesis.
Specimen part
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Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sex, Specimen part
View SamplesThe effect of a short-term calorie restricted diet was evaluated in heart in seven strains of mice
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sex, Specimen part
View SamplesThe effect of a short-term calorie restricted diet was evaluated in gastrocnemius muscle (GASTROC) in seven strains of mice
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sex, Specimen part
View SamplesThe effect of a short-term calorie restricted diet was evaluated in epididymal white adipose tissue (WAT) in seven strains of mice
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sex, Specimen part
View SamplesThe effect of a short-term calorie restricted diet was evaluated in cerebral cortex in seven strains of mice
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sex, Specimen part
View SamplesThe effect of a short-term calorie restricted diet was evaluated in six strains of mice
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Sex, Specimen part
View SamplesResveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg-1 day-1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles.
A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice.
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View SamplesDietary supplementation with -3 polyunsaturated fatty acids (-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 -3) and eicosapentaenoic acid (EPA; 20:5 -3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of -3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that -3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects.
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Sex
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