Human immunodeficiency virus type-1 Nef protein induces blood–brain barrier disruption in the rat: role of matrix metalloproteinase-9

Sporer, Bernd; Koedel, Uwe; Paul, Robert; Kohleisen, Birgit; Erfle, Volker; Fontana, Adriano; Pfister, Hans‐Walter

doi:10.1016/s0165-5728(99)00170-8

Cited by 74 publications

(46 citation statements)

References 33 publications

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“…25 These observations agree with the reported data in which MIP-1␣, MIP-1␤, and, to a lesser extent, RANTES promote the secretion of pro-MMP-9 by T lymphocytes. 57 The presence of MMP-9 was recently reported in the cerebrospinal fluid in HIV-infected patients 31 and in the rapid progressors group of simian immunodeficiency virus-infected monkeys. High expression of MMP-9 was correlated to both motor and cognitive deficits.…”

Section: Discussionmentioning

confidence: 88%

“…29 In addition, in vitro studies reported evidence that HIV itself, or at least the HIV Tat or Nef proteins directly promote MMP-9 secretion. [30][31][32] The principal aim of this study was to assess the importance of coreceptors, in some pathogenic pathways induced by their respective chemokine or gp120 ligands, without the participation of the CD4 receptor. We examined signal transduction in different cell types on cell incubation with soluble gp120s (X4-or R5-tropic HIV strains) or chemokines (stromal cell-derived factor 1 ␣ [SDF-1␣] or macrophage inflammatory protein 1 ␤ [MIP-1␤]).…”

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confidence: 99%

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HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

Missé

Estève

Renneboog

et al. 2001

Blood

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It has been previously shown that the HIV-1 envelope glycoprotein 120 (gp120) activates cell signaling by CXCR4, independently of CD4. The present study examines the involvement of different intracellular signaling pathways and their physiopathologic consequences following the CD4-independent interaction between CXCR4 or CCR5 and gp120 in different cell types: primary T cells, CD4 ؊ / CXCR4 ؉ /CCR5 ؉ T cells, or glioma cells. These interactions were compared with those obtained with natural ligands, stromal cell-derived factor 1 ␣ (SDF-1␣) (CXCL12) and macrophage inflammatory IntroductionAIDS results from different actions induced by HIV on its wide variety of target cells. The CD4 molecule is the major receptor of HIV-1. 1 The high-affinity binding of CD4 to glycoprotein 120 (gp120) 2 induces conformational changes in gp120 to allow its further binding to secondary receptors, 3-5 which could result in a trimolecular complex, CD4-gp120-coreceptor. 6,7 HIV coreceptors belong to the chemokine receptor family (see Baggiolini et al 8 for review), among which CXCR4 and CCR5 are the major attachment coreceptors for T-tropic and M-tropic isolates of HIV-1, respectively. 9,10 The HIV envelope binding to target cells induces activation through receptors, 11,12 eliciting functional responses that are important in AIDS pathogenesis. Although the cell activation is induced by a CD4-transconformed gp120 through the coreceptor, 13-15 a CD4-independent activation occurs, 16,17 particularly in T cells and cells from the central nervous system (CNS). 18,19 Indeed, it has been reported that cell signaling is activated by either the X4-tropic or R5-tropic HIV-1 envelopes, leading to activation of such functional responses as proliferation, differentiation, chemotaxis, 13,16 proinflammatory cytokines secretion, or apoptosis. 20,21 Apoptosis or programmed cell death is one of the major physiopathologic mechanisms of AIDS. Cells continuously stimulated become sensitive to apoptosis. 22 Interactions between 23 or between tumor necrosis factor ␣ (TNF␣) and its receptor (TNFr), activation of caspases, and down-regulation of the proto-oncogene Bcl2 protein and interleukin-2 (IL2) are considered the major apoptotic events during HIV infection leading to destruction of T cells, 24 macrophages, dendritic cells, and neurons.In the CNS, another important factor contributing to the neurodegenerative process is the presence of extracellular proteases from the matrix metalloproteinase (MMP) family. MMPs have been shown to degrade constituents of the extracellular matrix such as collagens, 25 favoring (1) The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S.C. section 1734. For personal use only. on April 4, 2019. by guest www.bloodjournal.org From destruction of the extracellular matrix in vivo or in vitro. 27 The presence of MMP-9 was reported in cerebrospinal fluid of HIVinfected patients. 26,2...

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

Missé

Estève

Renneboog

et al. 2001

Blood

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“…11,65,66 In vitro, Nef is lethal to neurons and glial cells in nanomolar concentrations and can increase the expression of MMPs, thus potentially modifying the permeability of the blood-brain barrier. 67,68 Nef has significant sequence homology with scorpion neurotoxins and like these venoms can cause the inactivation of a large-conductance potassium channels. [69][70][71] Based on these findings, it has been suggested that Nef contributes to the neuronal degeneration seen in HIV encephalitis.…”

Section: Neurotoxic Viral Proteinsmentioning

confidence: 99%

Cell death in HIV dementia

2005

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Many patients infected with human immunodeficiency virus type-1 (HIV-1) suffer cognitive impairment ranging from mild to severe (HIV dementia), which may result from neuronal death in the basal ganglia, cerebral cortex and hippocampus. HIV-1 does not kill neurons by infecting them. Instead, viral proteins released from infected glial cells, macrophages and/ or stem cells may directly kill neurons or may increase their vulnerability to other cell death stimuli. By binding to and/or indirectly activating cell surface receptors such as CXCR4 and the N-methyl-D-aspartate receptor, the HIV-1 proteins gp120 and Tat may trigger neuronal apoptosis and excitotoxicity as a result of oxidative stress, perturbed cellular calcium homeostasis and mitochondrial alterations. Membrane lipid metabolism and inflammation may also play important roles in determining whether neurons live or die in HIV-1-infected patients. Drugs and diets that target oxidative stress, excitotoxicity, inflammation and lipid metabolism are in development for the treatment of HIV-1 patients.

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“…[17][18][19][20][21] Therefore, it is possible that the circulating levels of MMP-9 reflect the increased susceptibility to cardiovascular diseases in HIV patients.…”

Section: Introductionmentioning

confidence: 99%

A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

et al. 2009

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We examined whether two functional polymorphisms (g.À1562C4T and g.À90(CA)14-24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.À90(CA)14-24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAARTinduced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.À1562C4T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications.

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Human immunodeficiency virus type-1 Nef protein induces blood–brain barrier disruption in the rat: role of matrix metalloproteinase-9

Cited by 74 publications

References 33 publications

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

HIV-1 glycoprotein 120 induces the MMP-9 cytopathogenic factor production that is abolished by inhibition of the p38 mitogen-activated protein kinase signaling pathway

Cell death in HIV dementia

A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients

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