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)

Infection of the central nervous system by the type 1 human immunodeficiency virus (HIV-1) commonly results in a number of neurological impairments known, in their most severe form, as HIV-associated dementia (HAD). The persistence of HIV encephalitis (HIVE), the pathological correlate of HAD, in spite of highly active antiretroviral therapy (HAART) underscores the importance of continued research focused on the neurobiology of HIV. To elucidate direct and indirect mechanisms of HIV neuropathogenesis, current investigation is focused on neuroinvasion, HIV-1-mediated mechanisms of neuronal damage and apoptosis, and compartmentalized evolution of virus in the brain. The aim of this review is to provide a selective overview of the most recent research on the neurobiology of HIV, adding only a brief introduction regarding established principles.
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PMID:Pathogenesis of human immunodeficiency virus-induced neurological disease. 1270 52

As the most numerous cells in the brain, astrocytes play a critical role in maintaining central nervous system homeostasis, and therefore, infection of astrocytes by human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) in vivo could have important consequences for the development of HIV encephalitis. In this study, we establish that astrocytes are infected in macaques during acute SIV infection (10 days postinoculation) and during terminal infection when there is evidence of SIV-induced encephalitis. Additionally, with primary adult rhesus macaque astrocytes in vitro, we demonstrate that the macrophage-tropic, neurovirulent viruses SIV/17E-Br and SIV/17E-Fr replicate efficiently in astrocytes, while the lymphocyte-tropic, nonneurovirulent virus SIV(mac)239 open-nef does not establish productive infection. Furthermore, aminoxypentane-RANTES abolishes virus replication, suggesting that these SIV strains utilize the chemokine receptor CCR5 for entry into astrocytes. Importantly, we show that SIV Nef is required for optimal replication in primary rhesus macaque astrocytes and that normalizing input virus by particle number rather than by infectivity reveals a disparity between the ability of a Nef-deficient virus and a virus encoding a nonmyristoylated form of Nef to replicate in these central nervous system cells. Since the myristoylated form of Nef has been implicated in functions such as CD4 and major histocompatibility complex I downregulation, kinase association, and enhancement of virion infectivity, these data suggest that an as yet unidentified function of Nef may exist to facilitate SIV replication in astrocytes that may have important implications for in vivo pathogenesis.
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PMID:Expression of simian immunodeficiency virus (SIV) nef in astrocytes during acute and terminal infection and requirement of nef for optimal replication of neurovirulent SIV in vitro. 1276 5

Highly active antiretroviral treatment (HAART), which has been available for most AIDS patients in France since 1996, has resulted in a dramatic improvement of the progression of the disease. From the survey of our series of 343 brains with acquired immunodeficiency syndrome (AIDS) from patients who died between 1985 and 2002, we found both quantitative and qualitative changes in the pattern of human immunodeficiency virus (HIV) neuropathology. Quantitatively, despite a dramatic decrease in the number of autopsies, brain involvement remained a major cause of death. There was an overall decrease in incidence of cerebral toxoplasmosis, cytomegalovirus encephalitis (CMVE), and HIV encephalitis (HIVE), for which successful treatment is available. This contrasted with the unchanged incidence of progressive multifocal leukoencephalopathy (PML) and malignant non-Hodgkin lymphomas (MNHL). However, when looking closer at the 3 last years, the incidence of diseases affecting patients with severe immunodepression (CMVE, PML, and MNHL) decreased between 2000 and 2002, whereas infections occurring in patients with milder immunodeficiency, toxoplasmosis, varicella-zoster encephalitis (VZVE), or herpes simplex virus encephalitis (HSVE) became more frequent. In addition, we found uncommon types of brain infection such as BK virus encephalitis or general paresis. Finally, we described new variants of HIVE: severe leukoencephalopathy with intense perivascular macrophage and lymphocyte infiltration, possibly due to an exaggerated response from a newly reconstituted immune system, and chronic "burnt out" forms of HIVE as VZVE, toxoplasmosis, or PML, possibly associated with prolonged survival, in which neither inflammation nor organisms could be detected. These findings are compared with those reported in other neuropathological studies from different developed countries.
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PMID:The changing pattern of HIV neuropathology in the HAART era. 1276 83

Reactive astrocytosis is a well-documented feature of HIV encephalitis (HIVE), but it is unclear whether restricted infection of astrocytes contributes to this phenomenon. In addition, the part played by reactive and/or infected astrocytes in AIDS-related dementia is not fully understood. In this study of patients at different stages of the human immunodeficiency virus (HIV) infection, who had been treated at most with one antiretroviral drug, reactive astrocytes were identified by immunopositivity for glial fibrillary acidic protein (GFAP) and infected astrocytes by positivity for HIV Nef protein. Results were compared for drug-using AIDS patients with (n=9) and without (n=7) HIVE, for presymptomatic HIV-positive drug users (n=12) and for control HIV-negative subjects (n=20), including a group who used drugs (n=10). GFAP-reactive astrocytes in both grey and white matter were significantly more numerous in HIVE subjects than in each of the other groups but did not correlate with viral load. Nef-positive astrocytes were confined to HIVE cases and to white matter, but were numerous in only one subject who was treatment-naive. Nef-positive microglia were identified in all HIVE cases and in occasional AIDS and presymptomatic subjects who did not have HIVE. The results suggest that astrocytes may form an additional viral reservoir in late HIV infection and may contribute to HIVE. However, the number of GFAP-positive astrocytes was neither increased in pre-AIDS nor in drug abuse, in contrast with microglia which we have shown previously to be up-regulated in both states.
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PMID:Relationship of Nef-positive and GFAP-reactive astrocytes to drug use in early and late HIV infection. 1288 98

Neurodegeneration, synaptic alterations, and gliosis are prominent features of human immunodeficiency virus (HIV) encephalitis, but HIV encephalitis is distinct from other viral encephalitides because neurodegeneration occurs in uninfected neurons at anatomical sites that are often distant from the site of viral replication. The HIV protein Tat is both neurotoxic and proinflammatory; however, its contribution to HIV-related synaptic dysfunction remains unknown. To determine the consequences of continuous Tat production in brain, we genetically engineered rat C6 glioma cells to stably produce Tat and stereotaxically infused these cells into the rat striatum or hippocampus. We discovered that HIV-Tat protein could be transported along anatomical pathways from the dentate gyrus to the CA3/4 region and from the striatum to the substantia nigra, resulting in behavioral abnormalities, neurotoxicity, and reactive gliosis. This demonstrates a unique neuronal transport property of a viral protein and establishes a mechanism for neuroglial dysfunction at sites distant from that of viral replication. Tat may thus be an important participant in brain dysfunction in HIV dementia.
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PMID:Synaptic transport of human immunodeficiency virus-Tat protein causes neurotoxicity and gliosis in rat brain. 1296 4

Human immunodeficiency virus (HIV) may be the cause of both primary and secondary brain diseases. In this review general features of HIV-associated neuropathology are discussed. Up to 90% of patients with AIDS have a variety of HIV-related brain diseases. Primary brain diseases including lymphocytic meningitis and HIV encephalitis are attributed directly to the effect of the virus on the brain. Secondary diseases including toxoplasmosis, cryptococcosis, primary leukoencephalopathies and lymphomas result from these patients' immunodeficiency status.
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PMID:[The central nervous system and HIV infection]. 1456 Jul 4

Changes that may appear in the central nervous system in the course of AIDS either result directly from HIV infection or--as is the case with opportunistic infections and some neoplasms--develop as a secondary consequence of general immunodeficiency. Neuroimaging techniques may be most useful in the differential diagnosis of these lesions. Basic principles of HIV encephalitis and progressive multifocal leukoencephalopathy differentiation in MRI scans are discussed in the paper, and diagnostic possibilities of MR imaging in some other infections (tuberculosis, toxoplasmosis, and cryptococcosis) are outlined. Special attention is paid, on the one hand, to difficulties in the differentiation between toxoplasmosis and lymphoma, and on the other hand--to the growing diagnostic utility of MR-spectroscopy in this respect.
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PMID:[CNS changes in HIV-infected patients: magnetic resonance spectroscopy]. 1456 Jul 5

Introduction of Highly Active Antiretroviral Treatment (HAART) which is available for most AIDS patients in France since 1996, has resulted in a dramatic improvement of the disease course. From the survey of our autopsy series of (AIDS) cases and the review of other neuropathological studies from different developed countries, we found quantitative and qualitative changes in the pattern of human immunodeficiency virus (HIV) neuropathology. Quantitatively, there was a dramatic decrease in the number of autopsy cases but brain involvement remained a major cause of death in AIDS patients. There was an overall decrease of cerebral toxoplasmosis, cytomegalovirus encephalitis (CMVE) and HIV encephalitis (HIVE) for which successful treatment is available. This contrasted with the unchanged incidence of progressive multifocal leucoencephalopathy (PML) and primary malignant non Hodgkin brain lymphomas (PMBL). However, when looking closer at the last three years, the incidence of diseases affecting patients with severe immunodepression (CMVE, PML, PMBL) decreased in 2000-2002, whereas infections occurring in patients with milder immunodeficiency (toxoplasmosis, varicella-zoster encephalitis (VZVE) or herpes simplex virus encephalitis (HSVE) became more frequent. Qualitatively, there were uncommon types of brain infections, such as BK virus encephalitis or general paresis. Finally, new forms of HIVE were reported: severe leukoencephalopathy with intense perivascular macrophage and lymphocyte infiltration possibly due to an exaggerated response from a newly reconstituted immune system; and also chronic "burnt out" forms of HIVE as VZVE, toxoplasmosis, or PML in which no inflammation and no infectious agent could be detected, likely due to prolonged survival.
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PMID:[The neuropathology of HIV infection in the era of highly active antiretroviral therapy]. 1475 84

The objective of this study was to determine whether host genetic polymorphisms influence the risk of developing human immunodeficiency virus (HIV) encephalitis and vacuolar myelopathy. Allelic association studies were carried out with common polymorphisms in candidate genes that are postulated to play a role in the pathogenesis of HIV-related neurologic complications. The authors studied brains and spinal cords from 270 patients who died of acquired immunodeficiency syndrome (AIDS) from 1989 to 1996. All had complete gross and microscopic pathologic evaluations, and the presence of microglial nodules, multinucleated giant cells, myelin pallor, and vacuolar myelopathy was assessed by an experienced neuropathologist who was blinded to the genotype. DNA was extracted from frozen brain samples, and determination of the presence of the APOE4, TNF-2, IL-1B*2, ILIRN*2 polymorphisms was determined by polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) mapping. The authors did not detect a consistent association between inheritance of candidate polymorphic alleles and the pathologic findings of HIV encephalitis or vacuolar myelopathy. Allelic association studies with candidate genes are powerful techniques that have the potential to contribute to understanding the pathophysiology of HIV-related neurodegeneration. This preliminary study, although including a substantial number of patients, was not sufficiently powered to exclude a modest but clinically significant effects. Future studies will require much larger sample sizes and technical advances to allow screening at larger number of candidate loci.
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PMID:Host genetic polymorphisms in human immunodeficiency virus-related neurologic disease. 1498 42

HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques result in encephalitis in approximately one-quarter of infected individuals and is characterized by infiltration of the brain with infected and activated macrophages. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (PK11195) is a ligand specific for the peripheral benzodiazepine receptor abundant on macrophages and is expressed in low levels in the noninfected brain. We hypothesized that positron-emission tomography (PET) with the carbon-11-labeled, R-enantiomer form of PK11195 ([(11)C](R)-PK11195) could image brain macrophages and hence the development of encephalitis in vivo. [(11)C](R)-PK11195 binding was assessed in the brain using PET in 11 SIV infected macaques, six of which showed increased binding in vivo. Postmortem examination of the brain in these six macaques demonstrated encephalitis, while macaques that did not show an increase in [(11)C](R)-PK11195 binding did not develop SIV encephalitis. Brain tissue from SIV encephalitic macaques also showed increased [(3)H](R)-PK11195 binding compared with binding in nonencephalitic macaques. Increased PK11195 binding in vivo and in postmortem brain tissue correlated with abundance of macrophages but not astrocytes. Our results suggest that PET [(11)C](R)-PK11195 imaging can detect the presence of macrophages in SIV encephalitis in vivo and may be useful to predict the development of HIV encephalitis and in studies of the pathogenesis and treatment of HIV dementia.
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PMID:PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS. 1505 4


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