Abstract
Nanoparticles derived from the elongated flexuous capsids of Turnip mosaic virus (TuMV) have been shown to be efficient tools for antibody sensing with a very high sensitivity if adequately functionalized with the corresponding epitopes. Taking advantage of this possibility, TuMV virus-like particles (VLPs) have been genetically derivatized with a peptide from the chaperonin Hsp60, a protein described to be involved in inflammation processes and autoimmune diseases. Antibodies against the peptide have been previously shown to have a diagnostic value in at least one autoimmune disease, multiple sclerosis. The functionalized Hsp60-VLPs showed their significant increase in sensing potency when compared to monoclonal antibody detection of the peptide in a conventional immunoassay. Additionally, the developed Hsp60-VLPs allowed the detection of autoantibodies against the Hsp60 peptide in an in vivo mouse model of dextran sodium sulfate (DSS)-induced colitis. The detection of minute amounts of the autoantibodies allowed us to perform the analysis of their evolution during the progression of the disease. The anti-Hsp60 autoantibody levels in the sera of the inflamed mice went down during the induction phase of the disease. Increased levels of the anti-HSP60 autoantibodies were detected during the resolution phase of the disease. An extension of a previously proposed model for the involvement of Hsp60 in inflammatory processes is considered, incorporating a role for Hsp60 autoantibodies. This, and related models, can now be experimentally tested thanks to the autoantibody detection hypersensitivity provided by the functionalized VLPs.
Highlights
The use of viral nanoparticles (VNPs) for biomedical applications has become a new tool in theranostics
We work with Turnip mosaic virus (TuMV), a virion with an elongated and flexuous structure, 700 nm long and 12 nm wide, with ca. 2000 copies of the coat protein in each particle, from which multifunctional VNPs can be obtained by genetic fusion and/or chemical conjugation to the coat protein (CP) [14,15,16,17]
Our first Heat Shock Protein 60 (Hsp60)-VNP derivatization approach was the production of virions genetically modified with the Hsp60-peptide fused to the CP N-terminus
Summary
The use of viral nanoparticles (VNPs) for biomedical applications has become a new tool in theranostics. Inflammatory bowel disease (IBD) is a pathology encompassing two chronic inflammatory disorders; Crohn s disease, characterized by transmural inflammation usually affecting the terminal ileus and/or the large intestine; and ulcerative colitis, where inflammation occurs in the lining of the colon mucosa [18,19]. In these pathologies, our research focuses on diagnosis improvement and the development of personalized therapy, in order to achieve improvement in the patients’ quality of life. This compound, when administered in drinking water, induces inflammation of the colon mucosa, as well as ulceration, which leads to severe weight loss and, in extreme cases, lethality
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