Monoclonal Antibodies to Phosphatidylinositol Phosphate Neutralize Human Immunodeficiency Virus Type 1: Role of Phosphate-Binding Subsites

Abstract

Both a murine monoclonal antibody to phosphatidylinositol phosphate (PIP) and a human monoclonal antibody (4E10) that is known to have broadly neutralizing capabilities against primary isolates of human immunodeficiency virus type 1 (HIV-1) bound to PIP, as determined by enzyme-linked immunosorbent assay. Each of the antibodies had antigen subsite binding specificities in aqueous medium for small phosphatecontaining molecules and for inositol. The anti-PIP monoclonal antibody inhibited infection by two HIV-1 primary isolates in neutralization assays employing primary human peripheral blood mononuclear cells. The data suggest that PIP or related lipids having free phosphates could serve as targets for the neutralization of HIV-1.

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

“…This inhibition might be dependent on cell type, the nature of the virus strain, and the assay conditions. The inhibitory effects of AC1 and AC8 cholesterol-specifi c antibodies on MDM and T-cells were comparable to those previously reported for antiphosphatidylinositol-4-phosphate antibody exhibiting neutralizing activity and blocking infection of PBMC by two primary isolates of HIV-1 and to the well-known broadly neutralizing 4E10 on PBMC ( 13 ).…”

“…Since in a recent work ( 13 ) another antilipid antibody, a mAb against phosphatidylinositol-4-phosphate, was reported to inhibit infection of peripheral blood mononuclear cells (PBMCs) with two HIV-1 primary isolates, we also investigated whether the new cholesterol-specifi c antibodies can affect in vitro HIV-1 infection/production of primary monocyte-derived macrophages (MDMs) and T-cells in cultures.…”

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

“…Those studies suggest that membrane proximity is not required for neutralization by 2F5. Interestingly, others have shown that 2F5 and 4E10 bind to phospholipids and to CL, a characteristic found in auto-Abs produced during antiphospholipid syndrome (2,25,97,200,201). Although a lipid binding function of these Abs may at first support the concept of membrane binding, the implications of these observations in the recognition of the MPER by 2F5 and 4E10 are not clear.…”

In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1

“…1B and Table 1), including two MAbs against the PID of gp41 that have been shown previously to capture HIV-1 efficiently. However, in addition to the three MPER MAbs, we also observed Envindependent capture of virions with MAbs 2G12 and D5, polyclonal Ab to HIV-1 p24, an MAb to human major histocompatibility complex (MHC-I), and two MAbs against lipids (CL15 [44,93] [␣-cardiolipin] and PIP4 [7] [␣-phosphatidylinositol phosphate]) and with the positive control capture agent, Galanthus nivalis lectin (Table 1). We note that in certain studies involving immobilized MAb VCAs, rather than directly immobilizing the capture MAb, microtiter wells were coated first with anti-Fc, and the capture MAb was immobilized via the anti-Fc, prior to the addition of virions (34,65).…”