New cholesterol-specific antibodies remodel HIV-1 target cells' surface and inhibit their in vitro virus production.
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 significant 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-specific antibodies on the target cells. This, in turn, may prevent the proper spatio-temporal juxtaposition of HIV-1 glycoproteins with CD4 and chemokine receptors, thus negatively interfering with virus attachment/entry.
Beck
Zoltán
Z
Institute of Medical Microbiology, University of Debrecen, H-4012, Debrecen, Hungary.
Balogh
Andrea
A
Kis
Andrea
A
Izsépi
Emese
E
Cervenak
László
L
László
Glória
G
Bíró
Adrienn
A
Liliom
Károly
K
Mocsár
Gábor
G
Vámosi
György
G
Füst
George
G
Matko
Janos
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000276:immunology* / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009068:Movement; D019718:Receptors, CXCR4 / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization; D014779:Virus Replication / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G; D019718:Receptors, CXCR4; D002784:Cholesterol