A cell adhesion peptide from foot-and-mouth disease virus can direct cell targeted delivery of a functional enzyme.
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.
Villaverde
A
A
Institut de Biologia Fonamental and Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. a.villaverde@cc.uab.es
Feliu
J X
JX
Arís
A
A
Harbottle
R P
RP
Benito
A
A
Coutelle
C
C
D000595:Amino Acid Sequence; D005537:Aphthovirus; D019149:Bioreactors; D002213:Capsid / Q000096:biosynthesis* / Q000737:chemistry; D036022:Capsid Proteins; D002448:Cell Adhesion; D004926:Escherichia coli / Q000201:enzymology; D005818:Genetic Engineering / Q000379:methods; D005822:Genetic Vectors; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D036022:Capsid Proteins; D008024:Ligands; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C442501:VP1 protein, Foot-and-mouth disease virus; D001616:beta-Galactosidase