Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions

J Virol. 1996 Jun;70(6):4045-52. doi: 10.1128/JVI.70.6.4045-4052.1996.

Abstract

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at high levels in Escherichia coli and spontaneously assembled into virus-like particles which could be readily purified. These fusion particles elicited high levels of both enzyme-linked immunosorbent assay- and FMDV-neutralizing antibodies in guinea pigs. The chimeric particles bound specifically to cultured eukaryotic cells. Mutant particles carrying the tripeptide sequence RGE in place of RGD and the use of a competitive peptide, GRGDS, confirmed the critical involvement of the RGD sequence in this binding. The chimeric particles also bound to purified integrins, and inhibition by chain-specific anti-integrin monoclonal antibodies implicated alpha 5 beta 1 as a candidate cell receptor for both the chimeric particle and FMDV. Some serotypes of FMDV bound to beta 1 integrins in solid- phase assays, and the chimeric particles competed with FMDV for binding to susceptible eukaryotic cells. Thus, HBc particles may provide a simple, general system for exploring the interactions of specific peptide sequences with cellular receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aphthovirus / physiology*
  • Cell Line
  • Female
  • Guinea Pigs
  • Hepatitis B Core Antigens
  • Hepatitis B virus / chemistry*
  • Humans
  • Integrins / metabolism*
  • Oligopeptides / metabolism*
  • Receptors, Virus / metabolism*
  • Recombinant Fusion Proteins / metabolism*
  • Viral Core Proteins / metabolism*

Substances

  • Hepatitis B Core Antigens
  • Integrins
  • Oligopeptides
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • Viral Core Proteins
  • arginyl-glycyl-aspartic acid