HIV-1, lipid rafts, and antibodies to liposomes: implications for anti-viral-neutralizing antibodies (Review)

Abstract

The human immunodeficiency virus type 1 (HIV-1) is an enveloped virus with a lipid bilayer that contains several glycoproteins that are anchored in, or closely associated with, the membrane surface. The envelope proteins have complex interactions with the lipids both on the host cells and on the target cells. The processes of budding from host cells and entry into target cells occur at sites on the plasma membrane, known as lipid rafts, that represent specialized regions that are rich in cholesterol and sphingolipids. Although the envelope glycoproteins are antigenic molecules that potentially might be used for development of broadly neutralizing antibodies in a vaccine to HIV-1, the development of such antibodies that have broad specificities against primary field isolates of virus has been largely thwarted to date by the ability of the envelope proteins to evade the immune system through various mechanisms. In this review, the interactions of HIV-1 with membrane lipids are summarized. Liposomes are commonly used as models for understanding interactions of proteins with membrane lipids; and liposomes have also been used both as carriers for vaccines, and as antigens for induction of antibodies to liposomal lipids. The possibility is proposed that liposomal lipids, or liposome-protein combinations, could be useful as antigens for inducing broadly neutralizing antibodies to HIV-1.

Induction of Antibodies Specific for Gp41 of HIV-1 by Gene Gun DNA Vaccination

“…Second, it remains unclear, whether the DNA immunisation generated the correct membrane associated context. HIV particles are budding from special regions of the cell membrane, so called rafts, that are characterised by specific lipid content [42] and it is unclear whether the DNA vaccines were also expressed in such a compartment. Third, conformational restrictions in the antigens expressed in vivo may have prevented the induction of neutralising antibodies.…”

Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes

“…The discovery of the novel lipid-binding properties of 2F5 and 4E10 has generated interest in the possibility that the binding of the antibodies to lipids themselves might participate as a part of the neutralizing mechanism of certain types of antibodies [17,22]. By utilizing liposomal methodology for inducing antibodies to lipids [23,24], a murine antiphosphatidylinositol-4-phosphate (anti-PIP) mAb (WR304) was produced that exhibited neutralization of infection by two primary HIV-1 isolates in a peripheral blood mononuclear cell (PBMC) assay but lacked any activity in the corresponding pseudovirus assay utilizing TZM-bl cells [25].…”

New cholesterol-specific antibodies remodel HIV-1 target cells’ surface and inhibit their in vitro virus production

“…As a novel aspect, this study points out that antilipid antibodies may act effectively not only on the virus but also on the target cell membrane, in contrast to the principle considered earlier in context of most neutralizing antibodies ( 26,27 ).…”

“…The fi ndings presented here may have an impact on the future development of HIV-1 specifi c vaccines as well ( 26 ). Recent data indicate that antibodies with membranepattern binding characteristics versus antibodies binding to one lipid or one protein may offer a better perspective to develop new, effi cient vaccine candidates ( 35 ).…”

“…They interfere most likely with the virus attachment. Although some mechanistic details of their action on target cells remain open, we believe that the inhibitory effect and the basic background mechanisms described herein may be helpful in further studies to clarify the cholesterol dependence of the attachment/entry mechanism, as well as may serve as a molecular basis for the development of new, combined lipid raft-oriented approaches in HIV-1 therapy ( 26 ).…”