AIDS Dementia Is Associated with Massive, Activated HIV-1 Infection and Concomitant Expression of Several Cytokines

Nuovo, Gerard J.; Alfieri, Mariaevelina

doi:10.1007/bf03401633

Cited by 116 publications

(86 citation statements)

References 18 publications

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“…[11][12][13][14] The rabies antibody (DF A II, Light Diagnostics, Temecula, CA, USA), is fluoroscein-tagged and was detected using an antifluoroscein-peroxidase conjugate. The antibody against TNFa (Chemicon Corporation, CA, USA) was unlabeled and detected using the BioGenex (San Ramon, CA, USA) Supersensitive kit.…”

Section: Viral Analysismentioning

confidence: 99%

“…[11][12][13][14] Briefly, optimal protease digestion time was determined using nonspecific incorporation of the reporter nucleotide digoxigenin dUTP. Optimal protease digestion is followed by overnight incubation in Rnase-free DNase (10 U per sample, Boehringer Mannheim, Indianopolis, IN, USA) and one-step RT/PCR using the rTth system and digoxigenin dUTP.…”

Section: Viral Analysismentioning

confidence: 99%

“…The chromogen is nitroblue tetrazolium and bromochloroindolyl phosphate (NBT/ BCIP) with nuclear fast red as the counterstain. The primer sequences for TNFa and iNOS were previously published 11,12 as were the primer sequences for suppressors of cytokine signaling (SOCS) expression. 14 The primer sequences for the rabies virus were: GAGTCACTCGAATATGTC, GT ATTGCCTCTCTAGCGG, CTACAATGGATGCCGAC, GACATGTCCGGAAGACTG.…”

Section: Viral Analysismentioning

confidence: 99%

“…Other viral encephalitis in humans, such as from HIV-1 infection, are marked by massive viral infection with concomitant expression of a variety of chemicals, including iNOS, TNFa, and a variety of interleukins. 11,12 Viral production appears to be synergistic with the production of cytokines such as TNFa that can cause neuronal damage, in that cytokine expression is mostly evident in noninfected cells present adjacent to cells which contain the virus. 11,12 The purpose of this study is to examine different diagnostic methodologies (histology, immunohistochemistry, and RT in situ PCR) for the detection of rabies encephalitis, and to elucidate the pathogenesis of this fatal disease by correlating viral production with cytokine expression.…”

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confidence: 99%

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Molecular detection of rabies encephalitis and correlation with cytokine expression

et al. 2005

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The purposes of this study were to elucidate the role of cytokine upregulation in the pathogenesis of rabies encephalitis and to compare the detection of Negri bodies with that of rabies protein by immunohistochemistry and rabies RNA by reverse transcriptase (RT) in situ PCR for its diagnosis. Negri bodies were evident in 4/7 of the documented rabies cases; viral protein and viral RNA were detected in each case. The average number of rabies-infected cells, determined by counting 150 neurons in serial sections in areas where viral protein was evident, with the three different detection methods was: Negri bodies (o1/150), immunohistochemistry (4/150), and RT in situ PCR (49/150). No rabies protein or RNA was detected in four control brain tissues that were read with the rabies cases in a blinded fashion. The ratio of cells expressing tumor necrosis factor a (TNFa) or inducible nitric oxide synthetase (iNOS) to 1 SSI-1/SOCS-1 (suppressors of cytokine signaling) expression, which is a novel class of negative feedback regulators of cytokine receptor signaling, was markedly increased only in the areas where many viral infected cells were present. Colabeling experiments showed that most of the cells expressing iNOS or TNFa were not virally infected, but rather adjacent to rabies-infected neurons. We conclude that RT in situ PCR for rabies virus is the most accurate test for the determination of viral load in rabies encephalitis. Further, the disease is characterized by massive viral infection of neurons in a markedly focal distribution in conjunction with a concomitant upregulation of cytokine expression in adjacent, noninfected cells that may be due, in part, to SOCS downregulation.

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Section: Viral Analysismentioning

confidence: 99%

Section: Viral Analysismentioning

confidence: 99%

Section: Viral Analysismentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular detection of rabies encephalitis and correlation with cytokine expression

et al. 2005

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“…Viral particles, however, are not the only mediators of CNS dysfunction and neuron toxicity. HIV-induced encephalitis is associated with immune activation of glial cells that results in alterations of normal cell biology, notably secretory functions (41)(42)(43)(44)(45). Improper regulation of these factors can lead to impaired cellular functioning, modified neurotransmitter action, amplified inflammation and neuronal damage.…”

Section: Macrophage Driven Pathogenesismentioning

confidence: 99%

Potentiation of excitotoxicity in HIV-1-associated Dementia and the significance of glutaminase

Erdmann¹,

Whitney²,

Zheng³

2006

Clinical Neuroscience Research

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HIV-1 Associated Dementia (HAD) is a significant consequence of HIV infection. Although multiple inflammatory factors contribute to this chronic, progressive dementia, excitotoxic damage appears to be an underlying mechanism in the neurodegenerative process. Excitotoxicity is a cumulative effect of multiple processes occurring in the CNS during HAD. The overstimulation of glutamate receptors, an increased vulnerability of neurons, and disrupted astrocyte support each potentiate excitotoxic damage to neurons. Recent evidence suggests that poorly controlled generation of glutamate by phosphate-activated glutaminase may contribute to the neurotoxic state typical of HAD as well as other neurodegenerative disorders. Glutaminase converts glutamine, a widely available substrate throughout the CNS to glutamate. Inflammatory conditions may precipitate unregulated activity of glutaminase, a potentially important mechanism in HAD pathogenesis.

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Potentiation ofN-methyl-D-aspartate-mediated neurotoxicity by immunostimulated murine microglia

Kim

1998

J. Neurosci. Res.

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Microglia have been shown to be immunostimulated by inflammatory cytokines and produce a number of toxic mediators. Here we report that immunostimulated microglia can synergistically enhance the N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity in rat cerebellar granule cells (CGC) in culture. Neurotoxicity was assessed by morphological examination and by measuring the release of lactate dehydrogenase and DNA fragmentation. Cultured microglia were immunostimulated by interferon-gamma (200 U/ml) and lipopolysaccharides (10 microg/ml) and one or two days later they were used for co-culture with CGC. Co-culture of CGC with immunostimulated microglia resulted in a remarkable enhancement of the NMDA receptor-mediated death of CGC. This enhanced neurotoxicity was mimicked by the nitric oxide releaser 3-morpholinosydnonimine (SIN-1) or S-nitroso-N-acetylpenicillamine (SNAP). Superoxide dismutase and catalase, which stabilise NO by removing superoxide anion, ameliorated the potentiation of the NMDA-mediated death of CGC in co-culture with immunostimulated microglia, implying that reactions of NO with superoxide to form peroxynitrite can be implicated in the potentiated neurotoxicity. Our data indicate that immunostimulated microglia, which may involve in various neuropathologies, potentiate the NMDA receptor-mediated excitotoxicity in part through the expression of inducible nitric oxide synthase.

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AIDS Dementia Is Associated with Massive, Activated HIV-1 Infection and Concomitant Expression of Several Cytokines

Abstract: These results suggest that two key elements in AIDS dementia are massive productive viral infection, involving microglia, neurons, and astrocytes, and concomitant stimulation of cytokine transcription in the neighboring uninfected cells.

Cited by 116 publications

References 18 publications

Molecular detection of rabies encephalitis and correlation with cytokine expression

Molecular detection of rabies encephalitis and correlation with cytokine expression

Potentiation of excitotoxicity in HIV-1-associated Dementia and the significance of glutaminase

Potentiation ofN-methyl-D-aspartate-mediated neurotoxicity by immunostimulated murine microglia

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