A novel peptide to disrupt the interaction of BST-2 and Vpu

Biopolymers. 2014 May;102(3):280-7. doi: 10.1002/bip.22488.

Abstract

Bone marrow stromal cell antigen 2 (BST-2) inhibits the release of HIV-1 and other enveloped viruses from the cell surface. HIV-1 Vpu binds to BST-2 through an interaction between transmembrane domains (TMD) of the two proteins and induces the downregulation of cell surface BST-2, thereby counteracting its antiviral activity. In this study, we designed and prepared a modified peptide BST2-TM-P1, which include the sequence of BST-2 TMD, keeping its property competing with BST-2 to bind with Vpu. Biological assay results indicate BST2-TM-P1 could increase the BST-2 level at the cell surface in Vpu dependent manner and significantly inhibit the replication of HIV-1 virion. Our studies indicate that blocking the interaction of Vpu and BST-2 is an effective way to combat HIV-1 infection.

Keywords: Vpu; anti-HIV-1; bone marrow stromal cell antigen 2; drug design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism*
  • Biological Assay
  • Cell Membrane / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • HeLa Cells
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Humans
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Binding / drug effects
  • Protein Structure, Tertiary
  • Quartz Crystal Microbalance Techniques
  • Solid-Phase Synthesis Techniques
  • Vesicular stomatitis Indiana virus / metabolism
  • Viral Envelope Proteins / metabolism
  • Viral Regulatory and Accessory Proteins / metabolism*
  • Virus Replication / drug effects

Substances

  • Antigens, CD
  • G protein, vesicular stomatitis virus
  • Human Immunodeficiency Virus Proteins
  • Membrane Glycoproteins
  • Peptides
  • Viral Envelope Proteins
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1