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

Mark Chambers, Gordon Dougan, John Newman, Fred Brown, John Crowther, A. Paul Mould, Martin J. Humphries, Michael J. Francis, Berwyn Clarke, Alan L. Brown, David Rowlands

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18 Citations (Scopus)

Abstract

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the el 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 α5β1 as a candidate cell receptor for both the chimeric particle and FMDV. Some serotypes of FMDV bound to β1 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.

Original languageEnglish
Pages (from-to)4045-4052
Number of pages8
JournalJournal of Virology
Volume70
Issue number6
Publication statusPublished - 1 Dec 1996
Externally publishedYes

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