Inhibition of Entry of HIV-1 in Neural Cell Lines by Antibodies Against Galactosyl Ceramide

Harouse, Janet M.; Bhat, Shama; Spitalnik, Steven L.; Laughlin, Mark; Stefano, Kelly; Silberberg, Donald H.; González‐Scarano, Francisco

doi:10.1126/science.1857969

Cited by 512 publications

(304 citation statements)

References 47 publications

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“…We found that D-54 cells express two classes of binding sites with higher (1.2 x 1 o-10 M) and lower (3.2 x 1o-9 M) affinity to rgp120. When compared with the results of Harouse et al ( 1991), our affinity data suggest that the high er affinity receptors consist of galactosyl-sulfatide and the lower affinity receptors of the trypsin-sensitive cell surface proteins. We also determined the binding of rgp 120 to trypsin-treated D-54 cells.…”

Section: Discussionmentioning

confidence: 55%

“…The human glioma cells did not express the main HIV-1 receptor CD4 as mRNA or as protein on their surfaces.lt has been described that several CD4-cells are susceptible to HIV-1, implicating the existence of additional HIV-1 receptors on neural cells (Ciapham et al, 1989;Harouse et al, 1989Harouse et al, , 1991Kozlowski et al, 1991;Li et al, 1990;Mizrachi et al, 1991;Schmitt et al, 1990). The only known molecular species expressed on the surface of D-54 cells capable of binding gp120 was found to be galactosyl-sulfatide.…”

Section: Discussionmentioning

confidence: 98%

“…The only known molecular species expressed on the surface of D-54 cells capable of binding gp120 was found to be galactosyl-sulfatide. A similar molecule, GaiC, has been described to bind rgp120 with an affinity of 1.16 x 1 o-10 M (Harouse et al, 1991), which is higher than the affinity of rgp 1 20 binding to CD4 (2-5 x 1 o-s M; Lasky et al, 1987). We found that D-54 cells express two classes of binding sites with higher (1.2 x 1 o-10 M) and lower (3.2 x 1o-9 M) affinity to rgp120.…”

Section: Discussionmentioning

confidence: 99%

“…GaiC and galactosyl-sulfatide have been found to bind HIV-1 gp120 as purified substances and on the surface of neural cells Harouse et al, 1991 ). Therefore, we determined the expression of GaiC and galactosyl-sulfatide on D-54 cells by immunofluorescent staining with monoclonal antibodies and flow cytometry.…”

Section: D-54 Glioma Cells Express Galactosyl-sulfatidementioning

confidence: 99%

“…lt was found that gp 120 does not only bind to the well-known CD4 molecules, but also to galactocerebroside (GaiC} and galactosyl-sulfatide, cellular membrane components expressed on the surface of oligodendrocytes and other neural cells (Harouse et al, 1991;Kuhlmann-Krieg et al, 1988;Ranscht et al, 1982). Polyclonal antibodies to GaiC can inhibit the entry of HIV-1 in neural celllines, suggesting that the binding of HIV to these membrane structures might be of biological significance Harouse et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase

Schneider-Schaulies¹,

Schneider‐Schaulies²,

Brinkmann³

et al. 1992

Virology

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Human immunodeficiency virus (HIV-1) infection in the human brain Ieads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp 120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on int~acellular.s.ignallin~. Herewe pre~ent evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatlde, spec1f1cally bmds to a protem receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) pre~ent. on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rap1dly 1nduced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130-and 115-kDa p~oteins. The c~ncentration of intracellular calciumwas not affected by rgp120 in these cells. Our data suggest a novel Signal transduc1ng HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: D-54 Glioma Cells Express Galactosyl-sulfatidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase

Schneider-Schaulies¹,

Schneider‐Schaulies²,

Brinkmann³

et al. 1992

Virology

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HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement

Bernardo¹,

Agresti²,

Levi³

1997

J. Neurosci. Res.

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The aim of this study was to assess whether the HIV protein gp120 can induce direct or/and indirect damage to oligodendrocytes (OL). Using highly purified cultures of rat OL, we report that gp120 binds to OL and induces functional alterations in these cells. Indeed, the percentage of cells expressing myelin basic protein (MBP) and the levels of all four MBP isoforms were substantially reduced after a 3-day treatment with 10 nM gp120. As gp120 depressed the ability of OL to reduce the tetrazolium salt MTT (a sign of mitochondrial impairment), the alteration of MBP production may be a consequence of decreased metabolic activity. The above effects were accompanied by a small increase in the number of apoptotic nuclei (from 4.3% in controls to 17.6% in cells treated for 3 days with gp120). As complement can lyse OL and gp120 is known to activate complement, we also studied the interaction between these two factors using OL cultures. The viral protein potentiated (by about 25%) the lytic effect of complement, when administered to the cultures 5 hr after complement, and depressed it (by about 30-40%), when added 5 hr before complement. Heat denaturation and anti-gp120 antibodies prevented the direct effect of gp120 on OL, but did not influence the interactions between gp120 and complement. Some gp120 non glycosylated peptides (V3 loop, 254-274 and 415-435 peptides) mimicked the ability of gp120 to antagonize the lytic effect of complement, but not that of potentiating complement lytic activity. In conclusion, our study indicates that gp120 can alter OL functional activity directly and can interfere with OL susceptibility to complement mediated lysis.

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Spermatozoon as a vehicle for HIV-1 and other viruses: A review

Piomboni

Baccetti

2000

Mol. Reprod. Dev.

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Inhibition of Entry of HIV-1 in Neural Cell Lines by Antibodies Against Galactosyl Ceramide

Cited by 512 publications

References 47 publications

HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase

HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase

HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement

Spermatozoon as a vehicle for HIV-1 and other viruses: A review

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