Characterization of a novel binding site for the human immunodeficiency virus type 1 envelope protein gp120 on human fetal astrocytes

Ma, Meihui; Geiger, Jonathan D.; Nath, Avindra

doi:10.1128/jvi.68.10.6824-6828.1994

Cited by 72 publications

(14 citation statements)

References 34 publications

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“…Studies with in situ polymerase chain reaction and laser capture dissection microscopy have confirmed that productive infection occurs exclusively within perivascular macrophages,113 and to a lesser extent in microglia, with restrictive or nonproductive infection of astrocytes 114, 115. Because CD4 is not present on astrocytes, this infection must be CD4 independent 116, 117. Neurons are not infected in humans, and regionally, most productive HIV infection is seen within the basal ganglia, brainstem, and deep white matter 118, 119.…”

Section: Diagnostic Studies In Handsmentioning

confidence: 99%

Human immunodeficiency virus‐associated neurocognitive disorders: Mind the gap

McArthur

Steiner

Sacktor

et al. 2010

Annals of Neurology

393

174

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Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs) remain among the most common disorders in people infected with HIV, even in an era when potent antiretroviral therapy is widely deployed. This review discusses the clinical features of HANDs and the implications for more effective treatment. With the improved survival of individuals treated with antiretrovirals, comorbid conditions are increasingly salient, including particularly coinfection with hepatitis C and the effects of aging. This review attempts to answer why there appears to be a therapeutic gap between the salutary effects of antiretroviral regimens and normalization of neurological function. A second gap is found in the understanding of the pathophysiology of HANDs. This review addresses this and discusses the animal models that have helped to elucidate these mechanisms. Although triggered by productive HIV infection of brain macrophages, aberrant and sustained immune activation appears to play a major role in inducing HANDs, and may explain the often incomplete neurological response to highly active antiretroviral therapy. Novel therapies aimed at persistent central nervous system inflammation will be needed to close this gap.

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Section: Diagnostic Studies In Handsmentioning

confidence: 99%

Human immunodeficiency virus‐associated neurocognitive disorders: Mind the gap

McArthur

Steiner

Sacktor

et al. 2010

Annals of Neurology

393

174

View full text Add to dashboard Cite

show abstract

“…These activated macrophages appear to secrete arachidonic acid, which perturbs the highaffinity excitatory amino acid uptake system of astrocytes. Nonetheless, it is likely that gp120 manifests additional actions, which may include direct effects on astrocytes, as recent reports have suggested (Ma et al, 1994;Codazzi et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

The Coat Protein gp120 of HIV‐1 Inhibits Astrocyte Uptake of Excitatory Amino Acids via Macrophage Arachidonic Acid

Dreyer

Lipton

1995

Eur J of Neuroscience

100

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The human immunodeficiency virus coat protein gp120 injures central mammalian neurons both in vitro and in vivo, and this observation may contribute, at least in part, to the neurological dysfunction associated with the acquired immunodeficiency syndrome. Recent work suggests that gp120 mediates neuronal damage predominantly via an indirect route involving activation of brain macrophages. We have previously shown that the stimulation of N-methyl-D-aspartate receptors by excitatory amino acids is essential for the neuronal injury observed with gp120. Here we show that gp120 impairs astrocyte uptake of excitatory amino acids and the excess glutamate thus engendered may contribute to the increased neuronal damage. We also studied the mechanism whereby gp120 inhibits the uptake of excitatory amino acids by astrocytes. We present data suggesting that at least one pathway involves a direct effect of gp120 on macrophages, which in turn release arachidonic acid, a known inhibitor of excitatory amino acid uptake by astrocytes. Our findings suggest that the observed effects on glia and neurons of gp120 may be secondary, at least in part, to its initial activation of macrophages.

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“…Human fetal brain tissue (gestational age, 13 to 16 weeks) was obtained with written consent from women undergoing elective termination of preg-nancy and with approval of the University of Manitoba Human Ethics Committee. Human fetal astrocyte and neuron cultures were prepared as described previously (19,20). Purity of astrocytes (Ͼ95%) and neurons (Ͼ70%) was determined by immunostaining for glial fibrillary acidic protein and microtubule-associated protein 2, respectively.…”

mentioning

confidence: 99%

Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells

Nath

1997

J Virol

Self Cite

184

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We measured the cellular uptake of 125 I-labeled full-length Tat (amino acids 1 to 86) (125 I-Tat 1-86) and 125 I-Tat 1-72 (first exon) in human fetal astrocytes, neuroblastoma cells, and human fetal neurons and demonstrated that the uptake of 125 I-Tat 1-72 without the second exon was much lower than that of 125 I-Tat 1-86 (P < 0.01). This suggests an important role for the C-terminal region of Tat for its cellular uptake. 125 I-Tat uptake could be inhibited by dextran sulfate and competitively inhibited by unlabeled Tat but not by overlapping 15-mer peptides, suggesting that Tat internalization is charge and conformationally dependent. Interestingly, one of 15-mer peptides, Tat 28-42 , greatly enhanced 125 I-Tat uptake. These findings are important for understanding the neuropathogenesis of human immunodeficiency virus type 1 infection and in the potential application of Tat for drug delivery to cells.

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Characterization of a novel binding site for the human immunodeficiency virus type 1 envelope protein gp120 on human fetal astrocytes

Cited by 72 publications

References 34 publications

Human immunodeficiency virus‐associated neurocognitive disorders: Mind the gap

Human immunodeficiency virus‐associated neurocognitive disorders: Mind the gap

The Coat Protein gp120 of HIV‐1 Inhibits Astrocyte Uptake of Excitatory Amino Acids via Macrophage Arachidonic Acid

Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells

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