Elongated Flexuous Plant Virus-Derived Nanoparticles Functionalized for Autoantibody Detection

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.

Turnip Mosaic Virus Coat Protein Deletion Mutants Allow Defining Dispensable Protein Domains for ‘in Planta’ eVLP Formation

“…The first construct is just wild type CP, whose plant-made eVLPs have already shown their usefulness in previous nanobiotechnological applications [ 19 , 20 ]. In this case, TuMV eVLPs-WT (wild-type) show a morphology similar to virion particles, with a helical symmetry and a size range of 700–1000 nm [ 25 ].…”

“…In addition to the fundamental nature of the knowledge about these CP–CP interactions, the information about them in eVLPs also has significant importance in the emerging area of the nanobiotechnological deployment of plant virus-derived nanoparticles [ 15 ]. In many instances virion functionalization is not advisable for biosafety reasons [ 16 , 17 , 18 ], and in other cases the modifications involved in functionalizations abolish virus infectivity [ 19 , 20 ], hence precluding their use. In most cases, these problems can be overcome by using functionalized eVLPs.…”

“…Thus far, most developments have been carried out in TuMV VNPs. For instance, selected peptides have been genetically fused between the first and second amino acid at the exposed N-terminal region, obtaining VNPs functionalized for different biotechnological applications [ 19 , 20 , 26 ]. Chemical functionalizations of TuMV VNPs have also been performed by click chemistry [ 27 ] or by crosslinking of the VNPs with an enzyme forming nanonets [ 28 ].…”

Virus-Based Nanomaterials and Nanostructures

“…The current Special Issue, including 11 original research works, focuses on highlighting the progress, challenges, and future directions in the area of virus-based nanomaterials and nanostructures with multiple applications in biomedicine and energy. Researchers have studied mineralization, magnetization, bioconjugation, and drug delivery for the development of biosensors and vaccines [6][7][8][9][10][11][12]. Research findings of virus-based biomimetic materials in energy, biosensors, and tissue regeneration over the last two decades are comprehensively discussed in reviews [13][14][15][16].…”

“…Yuste-Calvo et al developed turnip mosaic virus (TuMV)-based nanoparticles to detect antibodies with high sensitivity [7]. TuMV is a virion with an elongated and flexuous structure.…”