Synthetic Peptides and Anti-Peptide Antibodies as Probes to Study Interdomain Interactions Involved in Virus Assembly: The Envelope of the Human Immunodeficiency Virus (HIV-1)

Virology. 1992 May;188(1):1-13. doi: 10.1016/0042-6822(92)90729-9.

Abstract

Synthetic peptides and anti-peptide antibodies have been widely used as probes to map B- and T-cell epitopes on proteins. Such probes also have the potential to delineate contact sites involved generally in protein-protein interactions or in association of domains within a protein. We applied peptide/anti-peptide probes to define: (1) regions on the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp120 and gp41 involved in the association between these two glycoproteins; and (2) sites on gp120/gp41, essential for the association of HIV-1 with the CD4 cell receptor. Results of this examination suggested the following: (1) two segments on gp120, encompassing residues (102-126) and (425-452), contribute to the binding site for CD4 and are expected to be juxtaposed in the folded gp120 chain; (2) portions of immunodominant gp120 and gp41 epitopes, encompassing residues (303-338) and (579-611), respectively, appeared to be involved in the gp120-gp41 association, as suggested by direct binding studies and by the limited accessibility of these epitopes on HIV-1 virions: other portions of gp120 also appeared to contribute to the association between these two glycoproteins; (3) there is a partial overlap between gp41 and CD4 binding sites on gp120; (4) the fusion domain and a segment (637-666) of gp41 are not accessible to antibodies after oligomerization of gp41; and 5) the gp120-gp41 association was blocked by aurintricarboxylic acid, suggesting the possibility of developing antiviral compounds interfering with HIV-1 assembly.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Blotting, Western
  • CD4 Antigens / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology
  • HIV Antibodies* / immunology
  • HIV Envelope Protein gp120 / immunology
  • HIV Envelope Protein gp120 / physiology*
  • HIV Envelope Protein gp41 / immunology
  • HIV Envelope Protein gp41 / physiology*
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / metabolism
  • Molecular Sequence Data
  • Peptides* / chemical synthesis
  • Peptides* / immunology
  • Protein Binding
  • Radioimmunoassay

Substances

  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Immunodominant Epitopes
  • Peptides