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A cell adhesion peptide from foot-and-mouth disease virus can direct cell targeted delivery of a functional enzyme
A Villaverde1, J X Feliu, A Arís
1Institut de Biologia Fonamental and Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. a.villaverde@cc.uab.es
Abstract:
The G-H loop of foot-and-mouth disease virus is a disordered protrusion of the VP1 protein exposed on the virion surface. This short stretch includes an arginine-glycine-aspartic acid tripeptide, a recognized integrin-binding motif, which is responsible for cell attachment and infection. Eight copies of a peptide reproducing the amino acid sequence of this FMDV ligand have been displayed in solvent-exposed regions on an enzymatically active recombinant beta-galactosidase. This viral peptide segment enables the chimeric enzyme to bind mammalian cell lines with different efficiencies, probably depending on the number of suitable cell receptors present on each of them. Moreover, it also promotes the internalization of the attached enzyme, which is transiently active inside the cells. These results suggest further exploration of the potential use of short adhesion peptides of viral origin as cell attachment tags to direct the targeted delivery of both genes and enzymes, instead of whole, infectious viruses.
Insights
Researchers engineered a beta-galactosidase enzyme with a foot-and-mouth disease virus (FMDV) peptide. This modification allows the enzyme to bind and enter mammalian cells, suggesting potential for targeted gene and enzyme delivery.
Area of Science:
- Biochemistry
- Virology
- Molecular Biology
Background:
- The G-H loop of foot-and-mouth disease virus (FMDV) contains an arginine-glycine-aspartic acid (RGD) motif.
- This RGD motif is crucial for FMDV binding to cellular integrin receptors, mediating viral entry and infection.
Purpose of the Study:
- To investigate the potential of using viral adhesion peptides as cell-targeting moieties.
- To engineer a chimeric enzyme capable of binding and internalizing into mammalian cells.
Main Methods:
- A peptide mimicking the FMDV G-H loop RGD motif was synthesized.
- Eight copies of this peptide were displayed on a recombinant beta-galactosidase enzyme.
- The binding and internalization efficiency of the chimeric enzyme to mammalian cell lines were assessed.
Main Results:
- The chimeric beta-galactosidase successfully bound to mammalian cell lines.
- Binding efficiency varied among cell lines, correlating with receptor availability.
- The enzyme was internalized into cells and exhibited transient enzymatic activity.
Conclusions:
- Short viral adhesion peptides can mediate cell attachment and internalization.
- Engineered enzymes displaying viral peptides offer a potential strategy for targeted delivery of therapeutic agents.
- This approach could replace the use of whole viruses for gene and enzyme delivery.