Rapid Inflammasome Activation Following Mucosal SIV infection of Rhesus Monkeys
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens Macaca mulatta
PROVIDER: GSE80013 | GEO | 2016/05/01
SECONDARY ACCESSION(S): PRJNA317627
REPOSITORIES: GEO
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Project description:The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-? pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.
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2012-06-18 | E-GEOD-38795 | biostudies-arrayexpress
Project description:In this study, we investigated longitudinal changes in response to SIV infection of rhesus monkeys in the presence of morphine, compared to animals administered saline, before and after cART treatment. Using single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq), we examined the effect of morphine on brain-resident macrophages and microglia in these SIV-infected, cART-suppressed animals to better understand the factors responsible for the morphine-induced increased CNS reservoir and the role of opioids in neuropathogenesis.
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Project description:Cells from SIV-negative (SIVnegative_p17, n=5; SIVnegative_p18, n=5) and SIV-chronic (ChronicSIVinfection_p18, n=6) SP tissues were sorted for microarray studies. RNA samples were prepared using the Illumina beads station assay and hybridized to the Illumina HumanHT-12 version 4 Expression BeadChip according to the Illumina’s instruction. The data were normalized with the quantile normalization method of Bioconductor package limma . Missing values were imputed with R package impute (http://cran.rproject.org/web/packages/impute/index.html). Genes with significant differential expression levels were identified using Bioconductor limma package with >= 1.5 fold change (up or down), the false discovery rate (FDR) adjusted P value < 0.05.
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Project description:The virus/host interactions during the acute phase of human immunodeficiency virus (HIV) infection help determine the course of disease. During this time period, virus enters the brain. Here, we report clusters of genes whose transcripts are significantly upregulated in the frontal lobe of the brain during acute simian immunodeficiency virus (SIV) infection of rhesus monkeys. Many of these genes are involved in interferon (IFN) and/or interleukin (IL)-6 pathways. Although neither IFNa nor IFN? are elevated in the brain, IL6 is increased. Both IFNa and IL6 are elevated in plasma during this acute phase. The upregulation of STAT1, verified by immunohistochemical staining, can be due to both central nervous system (CNS) (SIV and IL6) and peripheral (IFNa and IL6) causes, and can itself drive the expression of many of these genes. Examination of the levels of expression of the upregulated genes in the post-acute and long-term phases of infection, as well as in SIV encephalitis, reveals increased expression throughout SIV infection, which may serve to protect the brain, but can have untoward long-term consequences.
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Project description:Question Addressed: How does Simian immunodeficiency virus (SIV) infection alter gene expression in memory CD4 T cell subsets very early during the 1st 10 days after infection? Memory CD4 T cells were sorted from rhesus macaque peripheral blood samples before infection and then at 4 and 10 days post SIV infection. RNA was recovered from the sorted memory CD4 T cells samples. RNA from the time point prior to SIV infection from each individual animal was used as the reference for the post SIV infection time points for that same animal. Thus, for each data set, the 4 and 10 day time points are being directly compared to the pre-infection data from the same animal. RNA samples as indicated above were used for reverse transcription reactions that directly incorporate Cy5 and Cy3 labeled nucleotides into the cDNA. Time: Time after infection with SIV
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