Gold manno-glyconanoparticles for intervening in HIV gp120 carbohydrate-mediated processes

Methods Enzymol. 2012:509:21-40. doi: 10.1016/B978-0-12-391858-1.00002-2.

Abstract

After nearly three decades since the discovery of human immunodeficiency virus (HIV) (1983), no effective vaccine or microbicide is available, and the virus continues to infect millions of people worldwide each year. HIV antiretroviral drugs reduce the death rate and improve the quality of life in infected patients, but they are not able to completely remove HIV from the body. The glycoprotein gp120, part of the envelope glycoprotein (Env) of HIV, is responsible for virus entry and infection of host cells. High-mannose type glycans that decorate gp120 are involved in different carbohydrate-mediated HIV binding. We have demonstrated that oligomannoside-coated gold nanoparticles (manno-GNPs) are able to interfere with HIV high-mannose glycan-mediated processes. In this chapter, we describe the methods for the preparation and characterization of manno-GNPs and the experiments performed by means of SPR and STD-NMR techniques to evaluate the ability of manno-GNPs to inhibit 2G12 antibody binding to gp120. The antibody 2G12-mediated HIV neutralization and the lectin DC-SIGN-mediated HIV trans-infection in cellular systems are also described.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Neutralizing
  • Binding, Competitive
  • Broadly Neutralizing Antibodies
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism
  • Gold / chemistry*
  • Gold / pharmacology
  • HIV Antibodies
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / physiology*
  • HIV Fusion Inhibitors / chemistry*
  • HIV Fusion Inhibitors / pharmacology
  • HIV Infections / prevention & control*
  • HIV-1 / drug effects
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / metabolism
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • Oligosaccharides / pharmacology
  • Particle Size
  • Protein Binding
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism
  • Surface Plasmon Resonance
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Titrimetry
  • Virus Internalization / drug effects

Substances

  • 2G12 monoclonal antibody
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Fusion Inhibitors
  • Lectins, C-Type
  • Oligosaccharides
  • Receptors, Cell Surface
  • gp120 protein, Human immunodeficiency virus 1
  • oligomannoside
  • Gold