The neuropathogenesis of HIV-1 infection

Gendelman, Howard E.; Lipton, Stuart A.; Tardieu, Marc; Bukrinsky, Michael; Nottet, Hans S.L.M.

doi:10.1002/jlb.56.3.389

Cited by 247 publications

(133 citation statements)

References 49 publications

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“…These resident macrophages of the brain are the ontogenetic and functional equivalent of macrophages in somatic tissues (29). Histopathological evidence suggests that microglia play an important role in the neuropathogenesis of HIV-1 infection within the CNS (30)(31)(32)(33). Permissive HIV-1 infection of the CNS occurs only in microglia, although astrocytes are also involved in HIV-1-related neuropathogenesis (34,35).…”

Section: Discussionmentioning

confidence: 99%

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

Chao

Gekker

et al. 1996

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

138

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Microglial cells, the resident macrophages of the brain, play an important role in the neuropathogenesis of human immunodeficiency virus type 1 (HIV-1), and recent studies suggest that opioid peptides regulate the function of macrophages from somatic tissues. We report herein the presence of ic opioid receptors (KORs) in human fetal microglia and inhibition of HIV-1 expression in acutely infected microglial cell cultures treated with KOR ligands. Using reverse transcriptase-polymerase chain reaction and sequencing analyses, we found that mRNA for the KOR was constitutively expressed in microglia and determined that the nucleotide sequence of the open reading frame was identical to that of the human brain KOR gene. The expression of KOR in microglial cells was confirmed by membrane binding of [31H]U69,593, a c-selective ligand, and by indirect immunofluorescence. Treatment of microglial cell cultures with U50,488 or U69,593 resulted in a dose-dependent inhibition of expression of the monocytotropic HIV-1 SF162 strain. This antiviral effect of the ic ligands was blocked by the specific KOR antagonist, nor-binaltrophimine. These findings suggest that c opioid agonists have immunomodulatory activity in the brain, and that these compounds could have potential in the treatment of HIV-1-associated encephalopathy.Activation of the three major types of opioid receptors (i.e., t,

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Section: Discussionmentioning

confidence: 99%

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

Chao

Gekker

et al. 1996

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

138

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“…There is, however, still no cure for the catastrophic consequence of SCI in paralyzed patients. Gendelman and Tardieu (15) have shown that trauma of the mature CNS leads to hypoxia-induced angiogenesis and infiltration of activated brain macrophages and neutrophils, all of which leads to scarring (16,17). Gliosis, the formation of a scar in injured CNS, involves hypoxia-driven inflammatory angiogenesis (18,19).…”

mentioning

confidence: 99%

“…Gliosis, the formation of a scar in injured CNS, involves hypoxia-driven inflammatory angiogenesis (18,19). Gliosis includes proliferation of astrocytes and microglia, and inflammatory infiltration of peripheral macrophages (15)(16)(17). CM101 is an antipathoangiogenic polysaccharide (20) derived from group B streptococcus (GBS) (21) that inhibits angiogenesis and subsequent infiltration of inflammatory cells and thereby formation of granulation tissue, which produces scarring (M. Neeman, R. Abramowitch, B.D.W., and C.G.H., unpublished data).…”

mentioning

confidence: 99%

CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury

Wamil

Hellerqvist

1998

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

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CM101, an antiangiogenic polysaccharide derived from group B streptococcus, was administered by i.v. injection 1 hr post-spinal-cord crush injury in an effort to prevent inflammatory angiogenesis and gliosis (scarring) in a mouse model. We postulated that gliosis would sterically prevent the reestablishment of neuronal connectivity; thus, treatment with CM101 was repeated every other day for five more infusions for the purpose of facilitating regeneration of neuronal function. Twenty-five of 26 mice treated with CM101 survived 28 days after surgery, and 24 of 26 recovered walking ability within 2–12 days. Only 6 of 14 mice in the control groups survived 24 hr after spinal cord injury, and none recovered function in paralyzed limbs. MRI analysis of injured untreated and treated animals showed that CM101 reduced the area of damage at the site of spinal cord compression, which was corroborated by histological analysis of spinal cord sections from treated and control animals. Electrophysiologic measurements on isolated central nervous system and neurons in culture showed that CM101 protected axons from Wallerian degeneration; reversed γ-aminobutyrate-mediated depolarization occurring in traumatized neurons; and improved recovery of neuronal conductivity of isolated central nervous system in culture.

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“…A recent study has shown that VIP can also prevent a similar NMDA-induced, nitric oxide-dependent injury in lung tissue (63). Elevated levels of quinolinate (64,65) and toxic products (including cytokines) released from macrophages/microglia have also been associated with increased levels of gp120 and may play a role in gp120 toxicity (55,59,60,66,67).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

Dibbern¹,

Glazner²,

Gozes³

et al. 1997

J. Clin. Invest.

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Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10 Ϫ 8 M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers.

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The neuropathogenesis of HIV-1 infection

Cited by 247 publications

References 49 publications

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression.

CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury

Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

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