Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The abnormal isoforms of the normal cellular prion protein (PrP), also termed Scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. The mRNA of PrP contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (HIV-1) cis-acting sequence TAR within the LTR; both structures contain the pentanucleotide CUGGG in the loop, and the uridine- and adenine-bulge in the stem. In this study, using purified HIV-encoded trans-activator, Tat, and HIV-1 TAR-RNA or PrP-mRNA containing the stem-loop structure, we demonstrate by use of gel-retardation and filter binding assays that Tat binds to TAR- and PrP-RNA with the dissociation constants of 2.9 or 37.0 nM, respectively, at a molar ratio of 0.7 mol of Tat to 1 mol of RNA fragment. The Tat-RNA (TAR or PrP) complexes bind to protein(s) in the nuclear matrix, isolated from human astrocytes (glial fibrillary acidic protein positive brain cells). Infection of astrocytes with HIV-1 resulted in an increased level of PrP mRNA. The data presented led us to assume that certain sequences in the PrP mRNA might be targets for proteins acting in trans.
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PMID:Accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus. 135 48

Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.
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PMID:Simultaneous detection of ferritin and HIV-1 in reactive microglia. 141 82

Among 102 brains obtained from patients with acquired immune deficiency syndrome (AIDS), 34 cases with subacute AIDS encephalitis were characterized by immunohistochemistry using an antibody that binds to a human immunodeficiency virus-1 (HIV-1) envelope glycoprotein, gp41. This glycoprotein was detected in mononucleated and/or multinucleated cells in 90% of adult and 50% of pediatric brains with subacute AIDS encephalitis. In addition, many gp41-positive cells with bipolar or multipolar processes were found in 10 cases, and these cells occurred most frequently in the basal ganglia and internal capsule. The phenotype of the gp41-positive cells was determined using an improved double-labeling immunohistochemical technique that employed beta-galactosidase and peroxidase conjugated reagents. Cell-type specific markers for double-labeling included: Ricinus communis agglutinin-1 (RCA-1) for macrophages and microglia; Ulex europaeus agglutinin-1 for endothelium; anti-glial fibrillary acidic protein (GFAP) for astrocytes; anti-amyloid precursor protein for neurons; and anti-leukocyte common antigen for leukocytes. Results of double-immunostaining revealed that gp41-positive cells of all morphologic types, including cells with bipolar or multipolar processes, were double-labeled with RCA-1, but not with markers for astrocytes, neurons, or endothelia. These findings support the contention that HIV-1 infection of the CNS is predominantly restricted to cells of the macrophage/microglia lineage.
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PMID:Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. 169 70

Primary human glial fibrillary acidic protein-positive (GFAP+) brain cells (enriched population) have successfully been infected with human immunodeficiency virus type 1 (HIV-1) in vitro, when cocultivated with HIV-1-producing H9 cells. Direct incubation of brain cells with HIV-1 resulted only in a limited infection. The percentage of HIV+ cells increased from 5% in passage 1 to 40% in passage 8. Simultaneously with the increase of infected cells, the reverse transcriptase activity in the culture medium increased and reached maximal values in passage 8. The infected cells also produced intact viral particles. In the early phase of cultivation the HIV-infected cells displayed a significantly higher proliferation rate than the uninfected controls. At passage number 8 the HIV-infected GFAP+ cells had almost totally lost the ability to grow, while the controls proliferated at a rate almost unimpaired from the beginning of the cultivation. Up to 10 to 15% of the HIV-infected GFAP+ cells contained at passage number 5 more than 3 nuclei. Memantine (1-amino-3,5-dimethyladamantane), a blocker of the N-methyl-D-aspartate receptor channels, was found to display a significant anti-HIV effect (at a concentration of 1 microgram/ml) on enriched cultures of GFAP+ cells in vitro.
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PMID:Susceptibility of primary human glial fibrillary acidic protein-positive brain cells to human immunodeficiency virus infection in vitro: anti-HIV activity of memantine. 170 44

The encephalopathy resulting from direct infection of the brain by human immunodeficiency virus (HIV), which correlates clinically with the AIDS dementia complex, has been reported as being localized to the white matter where it induces myelin loss, gliosis and perivascular infiltration by mononuclear macrophages and multinucleated giant cells. Damage to the cortical grey matter in HIV encephalopathy was investigated in nine randomly selected HIV-positive cases with or without clinical or morphological evidence of encephalopathy and in five age-matched controls, using routine histology and immunohistochemical methods [glial fibrillary acidic protein (GFAP), microglia and HIV antibodies]. Increased numbers of GFAP-expressing astrocytes and Ricinus communis agglutinin 1-120-expressing microglial cells were found in all the HIV-positive cases (including asymptomatic) and their severity could be correlated with the severity of the encephalopathy in the white matter; the increase in number of cells expressing GFAP was diffuse and the intensity of the staining higher than that of microglial cells. The subpial region was the most severely involved. It is suggested that involvement of the cortical grey matter is more common in HIV infection than previously suspected and that clinical evidence of a dementing process in AIDS is not necessarily due only to white matter lesions.
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PMID:The involvement of the cerebral cortex in human immunodeficiency virus encephalopathy: a morphological and immunohistochemical study. 208 94

The resting human microglia have previously been shown to be cells of dendritic morphology expressing class II MHC antigens and macrophage specific antigens by immunocytochemical techniques. To examine the relationship between the microglia and the family of dendritic antigen presenting cells (APC), normal white matter from eight normal adults with no neurological disease at autopsy was examined by immunocytochemical techniques to localize antibodies to leukocyte common antigen (LCA), HLA-DR, CD1 (T6), CD4 (T4), and glial fibrillary acidic protein. In addition, enzyme histochemical staining for ATPase, non-specific esterase (NSE), and acid phosphatase (ACP) was performed. The normal microglia are ATPase +ve, NSE -ve, ACP -ve, HLA-DR +ve, LCA +ve, CD1 (T6) +ve and weakly CD4 (T4) +ve. This specialized phenotype closely resembles that of Langerhans cells and suggests that microglia are not simply quiescent phagocytes, but may have a primary role as microenvironmentally specialized APC. The finding of weak anti-CD4 (T4) immunoreactivity supports suggestions for a central role for this cell in infection of the central nervous system by human immunodeficiency virus type 1.
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PMID:Microglial cells in human brain have phenotypic characteristics related to possible function as dendritic antigen presenting cells. 253 Mar 24

Six isolates of the human immunodeficiency virus (HIV) showed differences in their ability to productively infect glioma-derived cell lines and early-passage human brain cell cultures. Susceptibility to HIV infection correlated well with the expression of the astrocyte marker glial fibrillary acidic protein. The CD4 molecule was expressed on some, but not all, of the brain-derived cells; however, no correlation was observed between CD4 protein expression and susceptibility to virus infection. The results show that HIV can productively infect human brain cells, particularly those of glial origin, and suggest that these cell types in the brain can harbor the virus.
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PMID:Human immunodeficiency virus can productively infect cultured human glial cells. 347 22

Neurochemical, pathologic, virologic, and histochemical correlates of simian immunodeficiency virus (SIV)-associated central nervous system (CNS) dysfunction were assessed serially or at necropsy in rhesus monkeys that exhibited motor and cognitive deficits after SIV infection. Some infected monkeys presented with signs of acquired immunodeficiency disease (AIDS) at the time of sacrifice. Seven of eight animals exhibited motor skill impairment which was associated with elevated quinolinic acid in cerebrospinal fluid (CSF). Examination of the brains revealed diffuse increases in glial fibrillary acidic protein immunoreactivity in cerebral cortex in all animals, regardless of evidence of immunodeficiency disease. Reactive astrogliosis preceded or was coincident with the onset of neuropsychological impairments. Virus rescue from CSF of six of eight infected animals showed that one of three animals with AIDS and none of three animals without AIDS at necropsy had virus rescue-positive CSF. Multinucleated giant cells were seen in the brain of only one animal with end-stage AIDS and high systemic virus burden at death. Neither systemic nor CNS virus burden was associated with the onset of CNS dysfunction. SIV-associated motor/cognitive impairment is associated with subtle, widespread changes in CNS cytology and neurochemistry, rather than with large increases in brain virus burden or widespread virus-associated brain lesions.
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PMID:Cytopathologic and neurochemical correlates of progression to motor/cognitive impairment in SIV-infected rhesus monkeys. 812 May 38

The majority of AIDS patients will experience some degree of dementia induced by human immunodeficiency virus (HIV-1). In this study, we report that treatment of human brain tissue with envelope gp120 of HIV-1 did not cause neuronal death but did cause astrocyte alterations and/or death. Human astrocyte cultures showed decreased expression of glial fibrillary acidic protein (GFAP), as well as the diminution of a major protein of 66 kDa. These findings are similar to the in vitro changes observed when astrocytes are exposed to ammonia and in vivo changes observed in experimental hepatic encephalopathy. We hypothesize that AIDS dementia may partially involve a perturbation of astrocyte function by gp120 that could indirectly impair neuronal function.
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PMID:HIV-1 envelope gp120 alters astrocytes in human brain cultures. 831 70

The goal of our study was to assess whether the human immunodeficiency virus (HIV) coat protein gp120 induces functional alterations in astrocytes and microglia, known for their reactivity and involvement in most types of brain pathology. We hypothesized that gp120-induced anomalies in glial functions, if present, might be mediated by changes in the levels of intracellular messengers important for signal transduction, such as cAMP. Acute (10 min) exposure of cultured rat cortical astrocytes or microglia to 100 pM gp120 caused only a modest (50-60%), though statistically significant, elevation in cAMP levels, which was antagonized by the beta-adrenergic receptor antagonist propranolol. More importantly, the protein substantially depressed [by 30% (astrocytes) and 50% (microglia)] the large increase in cAMP induced by the beta-adrenergic agonist isoproterenol (10 nM), without affecting that induced by direct adenylate cyclase stimulation by forskolin. Qualitatively similar results were obtained using a glial fibrillary acidic protein (GFAP)-positive human glioma cell line. The depression of the beta-adrenergic response had functional consequences in both astrocytes and microglia. In astrocytes we studied the phosphorylation of the two major cytoskeletal proteins, vimentin and GFAP, which is normally stimulated by isoproterenol, and found that gp120 partially (40-50%) prevented such stimulation. In microglial cells, which are the major producers of inflammatory cytokines within the brain, gp120 partially antagonized the negative beta-adrenergic modulation of lipopolysaccharide (10 ng/ml)-induced production of tumor necrosis factor alpha. Our results suggest that, by interfering with the beta-adrenergic regulation of astrocytes and microglia, gp120 may alter astroglial "reactivity" and upset the delicate cytokine network responsible for the defense against viral and opportunistic infections.
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PMID:Human immunodeficiency virus coat protein gp120 inhibits the beta-adrenergic regulation of astroglial and microglial functions. 838 71


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