Project description:Molecular basis for CNS dysfunction in simian immunodeficiency virus-infected rhesus monkeys. We used microarrays to identify differentially expressed genes in chronic simian immunodeficiency virus-infected rhesus monkeys.
Project description:Molecular basis for CNS dysfunction in simian immunodeficiency virus-infected rhesus monkeys. We used microarrays to identify differentially expressed genes in chronic simian immunodeficiency virus-infected rhesus monkeys. Frontal lobe samples were obtained from control and SIV infected animals for RNA extraction and hybridization on Affymetrix microarrays. We sought to better understand the gene that changes in gene expression with SIV infection in the frontal lobe.
Project description:The etiology of the central nervous system (CNS) alterations after human immunodeficiency virus (HIV) infection, such as dementia and encephalitis, remains unknown. We have used microarray analysis in a monkey model of neuroAIDS to identify 98 genes, many previously unrecognized in lentiviral CNS pathogenesis, whose expression is significantly up-regulated in the frontal lobe of simian immunodeficiency virus-infected brains. Further, through immunohistochemical illumination, distinct classes of genes were found whose protein products localized to infiltrating macrophages, endothelial cells and resident glia, such as CD163, Glut5, and ISG15. In addition we found proteins induced in cortical neurons (ie, cyclin D3, tissue transglutaminase, 1-antichymotrypsin, and STAT1), which have not previously been described as participating in simian immunodeficiency virus or HIV-related CNS pathology. This molecular phenotyping in the infected brains revealed pathways promoting entry of macrophages into the brain and their subsequent detrimental effects on neurons. These data support the hypothesis that in HIV-induced CNS disease products of activated macrophages and astrocytes lead to CNS dysfunction by directly damaging neurons, as well as by induction of altered gene and protein expression profiles in neurons themselves which are deleterious to their function.
Project description:The etiology of the central nervous system (CNS) alterations after human immunodeficiency virus (HIV) infection, such as dementia and encephalitis, remains unknown. We have used microarray analysis in a monkey model of neuroAIDS to identify 98 genes, many previously unrecognized in lentiviral CNS pathogenesis, whose expression is significantly up-regulated in the frontal lobe of simian immunodeficiency virus-infected brains. Further, through immunohistochemical illumination, distinct classes of genes were found whose protein products localized to infiltrating macrophages, endothelial cells and resident glia, such as CD163, Glut5, and ISG15. In addition we found proteins induced in cortical neurons (ie, cyclin D3, tissue transglutaminase, 1-antichymotrypsin, and STAT1), which have not previously been described as participating in simian immunodeficiency virus or HIV-related CNS pathology. This molecular phenotyping in the infected brains revealed pathways promoting entry of macrophages into the brain and their subsequent detrimental effects on neurons. These data support the hypothesis that in HIV-induced CNS disease products of activated macrophages and astrocytes lead to CNS dysfunction by directly damaging neurons, as well as by induction of altered gene and protein expression profiles in neurons themselves which are deleterious to their function. Keywords = HIV dementia Keywords = Gene array Keywords = Simian immunodeficiency virus Keywords = rhesus macaque Keywords: other
Project description:Chronic binge alcohol administration accentuates expression of pro-fibrotic and inflammatory genes in the skeletal muscle of simian immunodeficiency virus-infected macaques
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. Keywords = HIV dementia Keywords = Gene array Keywords = Cytokine Keywords = Simian immunodeficiency virus Keywords: other
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.