New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production

Zoltán Beck, Andrea Balogh, Andrea Kis, Emese Izsépi, L. Cervenák, Glória László, Adrienn Bíró, K. Liliom, Gábor Mocśr, G. Vámosi, G. Füst, J. Matkó

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The importance of membrane rafts in HIV-1 infection is still in the focus of interest. Here, we report that new monoclonal anticholesterol IgG antibodies (ACHAs), recognizing clustered membrane cholesterol (e.g., in lipid rafts), rearrange the lateral molecular organization of HIV-1 receptors and coreceptors in the plasma membrane of HIV-1 permissive human T-cells and macrophages. This remodeling is accompanied with a substantial inhibition of their infection and HIV-1 production in vitro. ACHAs promote the association of CXCR4 with both CD4 and lipid rafts, consistent with the decreased lateral mobility of CXCR4, while Fab fragments of ACHAs do not show these effects. ACHAs do not directly mask the extracellular domains of either CD4 or CXCR4 nor do they affect CXCR4 internalization. No signifi cant inhibition of HIV production is seen when the virus is preincubated with the antibodies prior to infection. Thus, we propose that the observed inhibition is mainly due to the membrane remodeling induced by cholesterol-specifi c antibodies on the target cells. This, in turn, may prevent the proper spatiooral juxtaposition of HIV-1 glycoproteins with CD4 and chemokine receptors, thus negatively interfering with virus attachment/ entry.-Beck, Z., A. Balogh, A. Kis, E. Izsépi, L. Cervenak, G. László, A. Bíró, K. Liliom, G. Mocsár, G. Vámosi, G. Füst, and J. Matko. New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production.

Original languageEnglish
Pages (from-to)286-296
Number of pages11
JournalJournal of Lipid Research
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 1 2010

Fingerprint

HIV Antibodies
Viruses
HIV-1
Cholesterol
Antibodies
Immunoglobulin G
Membranes
HIV Receptors
Lipids
CD4 Antigens
Immunoglobulin Fab Fragments
T-cells
Macrophages
Chemokine Receptors
Virus Attachment
Virus Internalization
Cell membranes
Masks
Infection
In Vitro Techniques

Keywords

  • Cholesterolspecifi c IgG
  • HIV-1 production
  • HIV-1 receptors
  • Lipid rafts
  • Membrane cholesterol
  • Monocyte-macrophage cells
  • T-cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production. / Beck, Zoltán; Balogh, Andrea; Kis, Andrea; Izsépi, Emese; Cervenák, L.; László, Glória; Bíró, Adrienn; Liliom, K.; Mocśr, Gábor; Vámosi, G.; Füst, G.; Matkó, J.

In: Journal of Lipid Research, Vol. 51, No. 2, 01.02.2010, p. 286-296.

Research output: Contribution to journalArticle

Beck, Zoltán ; Balogh, Andrea ; Kis, Andrea ; Izsépi, Emese ; Cervenák, L. ; László, Glória ; Bíró, Adrienn ; Liliom, K. ; Mocśr, Gábor ; Vámosi, G. ; Füst, G. ; Matkó, J. / New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production. In: Journal of Lipid Research. 2010 ; Vol. 51, No. 2. pp. 286-296.
@article{7ecc6f8aef4e4e8cafe9cedb63572a2c,
title = "New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production",
abstract = "The importance of membrane rafts in HIV-1 infection is still in the focus of interest. Here, we report that new monoclonal anticholesterol IgG antibodies (ACHAs), recognizing clustered membrane cholesterol (e.g., in lipid rafts), rearrange the lateral molecular organization of HIV-1 receptors and coreceptors in the plasma membrane of HIV-1 permissive human T-cells and macrophages. This remodeling is accompanied with a substantial inhibition of their infection and HIV-1 production in vitro. ACHAs promote the association of CXCR4 with both CD4 and lipid rafts, consistent with the decreased lateral mobility of CXCR4, while Fab fragments of ACHAs do not show these effects. ACHAs do not directly mask the extracellular domains of either CD4 or CXCR4 nor do they affect CXCR4 internalization. No signifi cant inhibition of HIV production is seen when the virus is preincubated with the antibodies prior to infection. Thus, we propose that the observed inhibition is mainly due to the membrane remodeling induced by cholesterol-specifi c antibodies on the target cells. This, in turn, may prevent the proper spatiooral juxtaposition of HIV-1 glycoproteins with CD4 and chemokine receptors, thus negatively interfering with virus attachment/ entry.-Beck, Z., A. Balogh, A. Kis, E. Izs{\'e}pi, L. Cervenak, G. L{\'a}szl{\'o}, A. B{\'i}r{\'o}, K. Liliom, G. Mocs{\'a}r, G. V{\'a}mosi, G. F{\"u}st, and J. Matko. New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production.",
keywords = "Cholesterolspecifi c IgG, HIV-1 production, HIV-1 receptors, Lipid rafts, Membrane cholesterol, Monocyte-macrophage cells, T-cells",
author = "Zolt{\'a}n Beck and Andrea Balogh and Andrea Kis and Emese Izs{\'e}pi and L. Cerven{\'a}k and Gl{\'o}ria L{\'a}szl{\'o} and Adrienn B{\'i}r{\'o} and K. Liliom and G{\'a}bor Mocśr and G. V{\'a}mosi and G. F{\"u}st and J. Matk{\'o}",
year = "2010",
month = "2",
day = "1",
doi = "10.1194/jlr.M000372",
language = "English",
volume = "51",
pages = "286--296",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "2",

}

TY - JOUR

T1 - New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production

AU - Beck, Zoltán

AU - Balogh, Andrea

AU - Kis, Andrea

AU - Izsépi, Emese

AU - Cervenák, L.

AU - László, Glória

AU - Bíró, Adrienn

AU - Liliom, K.

AU - Mocśr, Gábor

AU - Vámosi, G.

AU - Füst, G.

AU - Matkó, J.

PY - 2010/2/1

Y1 - 2010/2/1

N2 - The importance of membrane rafts in HIV-1 infection is still in the focus of interest. Here, we report that new monoclonal anticholesterol IgG antibodies (ACHAs), recognizing clustered membrane cholesterol (e.g., in lipid rafts), rearrange the lateral molecular organization of HIV-1 receptors and coreceptors in the plasma membrane of HIV-1 permissive human T-cells and macrophages. This remodeling is accompanied with a substantial inhibition of their infection and HIV-1 production in vitro. ACHAs promote the association of CXCR4 with both CD4 and lipid rafts, consistent with the decreased lateral mobility of CXCR4, while Fab fragments of ACHAs do not show these effects. ACHAs do not directly mask the extracellular domains of either CD4 or CXCR4 nor do they affect CXCR4 internalization. No signifi cant inhibition of HIV production is seen when the virus is preincubated with the antibodies prior to infection. Thus, we propose that the observed inhibition is mainly due to the membrane remodeling induced by cholesterol-specifi c antibodies on the target cells. This, in turn, may prevent the proper spatiooral juxtaposition of HIV-1 glycoproteins with CD4 and chemokine receptors, thus negatively interfering with virus attachment/ entry.-Beck, Z., A. Balogh, A. Kis, E. Izsépi, L. Cervenak, G. László, A. Bíró, K. Liliom, G. Mocsár, G. Vámosi, G. Füst, and J. Matko. New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production.

AB - The importance of membrane rafts in HIV-1 infection is still in the focus of interest. Here, we report that new monoclonal anticholesterol IgG antibodies (ACHAs), recognizing clustered membrane cholesterol (e.g., in lipid rafts), rearrange the lateral molecular organization of HIV-1 receptors and coreceptors in the plasma membrane of HIV-1 permissive human T-cells and macrophages. This remodeling is accompanied with a substantial inhibition of their infection and HIV-1 production in vitro. ACHAs promote the association of CXCR4 with both CD4 and lipid rafts, consistent with the decreased lateral mobility of CXCR4, while Fab fragments of ACHAs do not show these effects. ACHAs do not directly mask the extracellular domains of either CD4 or CXCR4 nor do they affect CXCR4 internalization. No signifi cant inhibition of HIV production is seen when the virus is preincubated with the antibodies prior to infection. Thus, we propose that the observed inhibition is mainly due to the membrane remodeling induced by cholesterol-specifi c antibodies on the target cells. This, in turn, may prevent the proper spatiooral juxtaposition of HIV-1 glycoproteins with CD4 and chemokine receptors, thus negatively interfering with virus attachment/ entry.-Beck, Z., A. Balogh, A. Kis, E. Izsépi, L. Cervenak, G. László, A. Bíró, K. Liliom, G. Mocsár, G. Vámosi, G. Füst, and J. Matko. New cholesterol-specifi c antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production.

KW - Cholesterolspecifi c IgG

KW - HIV-1 production

KW - HIV-1 receptors

KW - Lipid rafts

KW - Membrane cholesterol

KW - Monocyte-macrophage cells

KW - T-cells

UR - http://www.scopus.com/inward/record.url?scp=77949503413&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949503413&partnerID=8YFLogxK

U2 - 10.1194/jlr.M000372

DO - 10.1194/jlr.M000372

M3 - Article

C2 - 19654424

AN - SCOPUS:77949503413

VL - 51

SP - 286

EP - 296

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 2

ER -