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Title: CHIMERIC HEPATITIS B VIRUS CORE PARTICLES AS PROBES FOR STUDYING PEPTIDE-INTEGRIN INTERACTIONS

Author
item CHAMBERS, MARK - TECH & MEDICINE, LONDON
item DOUGAN, GORDON - TECH & MEDICINE, LONDON
item Newman, John
item Brown, Fred
item CROWTHER, JOHN - ANIMAL HEALTH, PIRBRIGHT
item MOULD, A - UNIVERSITY OF MANCHESTER
item HUMPHRIES, MARTIN - UNIVERSITY OF MANCHESTER
item FRANCIS, MICHAEL - WELLCOME RESEARCH LABS
item CLARKE, BERWYN - WELLCOME RESEARCH LABS
item ROWLANDS, DAVID - WELLCOME RESEARCH LABS

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/12/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: The sequence arginine, glycine, aspartic acid at positions 145, 146 and 147 on protein VP1 is involved in the attachment of foot-and-mouth disease virus to susceptible cells. This sequence is located on the immunodominant loop of the virus particle. Previous work by others had indicated that the virus attachment to susceptible cells via the alpha-V-Beta-3 integrin receptor. This work shows that other receptors, notably alpha-5-Beta-1, are also involved in attachment.

Technical 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 enzymed-linked immunosorbent assay- and FMDV-neutralizing antibodies and 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 particles 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.