Quantification of the CD55 and CD59, Membrane Inhibitors of Complement on HIV‐1 Particles as a Function of Complement‐Mediated Virolysis

Abstract

Previous studies have demonstrated that the murine monoclonal antibody (MoAb) NM-01 activates the human complement classical pathway resulting in lysis of human immunodeficiency virus (HIV). The present study was performed to determine the availability of the V3-loop of gp120 relative to the complement regulatory proteins, CD55 (DAF) and CD59 (HRF20) molecules on HIV. The results demonstrate that CD55 and CD59 exist on HIV virions, along with gp120 molecules. These findings suggest that activation of human complement on free viral particles is induced by MoAb NM-01 and that this occurs regardless of the presence of CD55 and CD59 molecules. The destruction of viral particles was demonstrated by a decrease in infectivity. The involvement of human complement in this process was confirmed with an immunoelectron microscopy technique by the presence of a human C9 to prove membrane attack complex (MAC). The results indicate that NM-01 can induce complement activation because of the ratios of CD55 and CD59 to gp120 molecules on HIV virions. The availability of the gp120 V3 domain on the virion is sufficient for binding of NM-01 and thereby the formation of MAC that results in virolysis.

Cholesterol Depletion of Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus with β-Cyclodextrin Inactivates and Permeabilizes the Virions: Evidence for Virion-Associated Lipid Rafts

“…Three-dimensional reconstruction of transmission electron microscopy images or other ultrastructural approaches will be necessary to clarify this important issue. Other evidence for lipid rafts on HIV-1 virion particles comes from electron microscopy studies showing localization of GPI-anchored proteins CD55 (DAF) and CD59 to one pole of the virions (36). A caveat is that the processing of virions in these earlier studies may have induced capping or clustering of the molecules as can occur in cells.…”

Update on Fc-Mediated Antibody Functions Against HIV-1 Beyond Neutralization

“…Indeed, the gp120 Env does not bind complement (168). Moreover, during budding, HIV incorporates glycosyl phosphatidylinositol (GPI)anchored CD55 and CD59 as well as transmembrane CD46, which are downregulatory molecules that inhibit complementmediated damage to the virus (169). HIV also captures serum complement factor H, which plays a central role in protecting cells from complement by downregulating complement binding and in turn increases virulence (170)(171)(172).…”

Gag Induces the Coalescence of Clustered Lipid Rafts and Tetraspanin-Enriched Microdomains at HIV-1 Assembly Sites on the Plasma Membrane

“…Proteomics, lipidomics, and biochemical studies have shown that the HIV-1 envelope is enriched in lipids and proteins that are also markers for lipid rafts (3,11,16,21,48,96,109,119), and envelope lipids appear ordered like those in rafts (90). Immunofluorescence microscopy studies have revealed that Gag colocalizes/copatches with lipid raft markers in cells (59,98,105) and cofractionates with lipid raft markers in detergent-resistant membranes (DRMs) (9,31,32,53,59,84,85,98,104,107) although qualitative differences between canonical DRMs and Gag-containing DRMs have been noted (31,59,84).…”