Structurally driven selection of human hepatitis C virus mimotopes.
A structural genomics approach is proposed for the development of new diagnostic kits. It combines molecular modelling, peptide synthesis and immunological tests. The preliminary step is the development of a reliable three-dimensional structure of an immunodominant protein of the target pathogenic organism using the various bioinformatic strategies that are now available to structural biologists. Once the protein structure is obtained, the most surface-exposed fragments with minimal sequence variability among the different strains reported in the genomic data bank are reproduced synthetically as linear peptides. These peptides are then tested for immunoreactivity with the plasma of infected patients to determine whether the synthetic molecules have antigenic activity and can therefore be used to detect infecting agents. This structurally driven selection of mimotopes was successfully performed for the human hepatitis C virus, as five peptides that specifically interact with the plasma of HCV-infected patients were identified solely on the basis of the three-dimensional structure predicted for the E2 homodimer of the la viral subtype. A similar approach could easily be extended to a large variety of immunogenic proteins from other pathogenic organisms.
Spiga
Ottavia
O
Biomolecular Structure Research Center and Department of Molecular Biology, University of Siena, Siena, Italy.
Padula
Maria G
MG
Scarselli
Maria
M
Ciutti
Arianna
A
Bernini
Andrea
A
Venditti
Vincenzo
V
Prischi
Filippo
F
Falciani
Chiara
C
Lozzi
Luisa
L
Bracci
Luisa
L
Valensin
Piero E
PE
Caudai
Cinzia
C
Niccolai
Neri
N
D004797:Enzyme-Linked Immunosorbent Assay; D005814:Genes, Viral; D016174:Hepacivirus / Q000737:chemistry* / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012641:Selection, Genetic; D016415:Sequence Alignment; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics; D014764:Viral Proteins / Q000138:chemical synthesis / Q000276:immunology
D007106:Immune Sera; D010455:Peptides; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C091015:glycoprotein E2, Hepatitis C virus