Neurological Aspects of Human Immunodeficiency Virus Infection

Gendelman, Howard E.; Gendelman, Seymour

doi:10.1007/978-1-4684-5886-2_12

Cited by 9 publications

(7 citation statements)

References 138 publications

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“…Macrophage tropism may be essential for HIV-1 (and SIV) neuroinvasiveness (38,39 (8,9,40). Similar pathology was not observed in grafts infected with cell-free HIV-1, suggesting that direct cell-to-cell contact of HIV-1-infected macrophages with neural cells or, alternatively, the local release of cytokines or other neurotoxic factors may be required for neuronal damage.…”

Section: Discussionmentioning

confidence: 98%

Human immunodeficiency virus type 1 infection of neural xenografts.

Cvetkovich

Lazar

Blumberg

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a bloodbrain barrier, and differentiated, forming neurons and glia.

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Section: Discussionmentioning

confidence: 98%

Human immunodeficiency virus type 1 infection of neural xenografts.

Cvetkovich

Lazar

Blumberg

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…Proposed theories of CNS dysfunction abound. These include: coexistence of opportunistic CNS infections (21,22), secretory toxic factors from infected monocytes, gpl20mediated neuronal growth factor blockade or killing, and neurotoxicity by HIV tat or other viral regulatory components. All or any of these mechanisms may result in cytotoxic effects in neurons and/or oligodendrocytes (23)(24)(25).…”

mentioning

confidence: 99%

Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease.

Genis

Jett

Bernton

et al. 1992

The Journal of Experimental Medicine

498

286

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Stlmmsr~Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-l^D^-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-o 0 and interleukin 1B (IblB) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-B, Iblc~, IL-6, interferon c~ (IFN-c~), and IFN-'y were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, >2.5-fold, the levels of TNF-o~. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes.

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“…Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) results in cognitive and motor abnormalities in a majority of infected individuals. HIV-1-associated dementia or AIDS dementia complex (ADC), a devastating complication of direct viral infection of the brain, arguably represents one of the most severe and significant clinical manifestations of HIV infection (6,13,16,26,43). The pathological hallmarks coincident with cognitive and motor dysfunctions include HIV-1 infection of brain macrophages, microglia, and multinucleated giant cells; astrocyte proliferation; and neuronal loss in discrete areas of the retina, neocortex, and subcortical brain (14,18,29,40,49,50,53,59,60).…”

mentioning

confidence: 99%

Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin

Gelbard

Nottet

Swindells

et al. 1994

J Virol

300

100

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The pathogenesis of central nervous system disease during human immunodeficiency virus type 1 (HIV-1) infection revolves around productive viral infection of brain macrophages and microglia. Neuronal losses in the cortex and subcortical gray matter accompany macrophage infection. The question of how viral infection of brain macrophages ultimately leads to central nervous system (CNS) pathology remains unanswered. Our previous work demonstrated high-level production of tumor necrosis factor alpha, interleukin 1 , arachidonic acid metabolites, and platelet-activating factor (PAF) from HIV-infected monocytes and astroglia (H.

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Neurological Aspects of Human Immunodeficiency Virus Infection

Cited by 9 publications

References 138 publications

Human immunodeficiency virus type 1 infection of neural xenografts.

Human immunodeficiency virus type 1 infection of neural xenografts.

Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease.

Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin

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