Therapeutic Potential of Engineered Virus-like Particles of Parvovirus B19

Abstract

Virus-like particles (VLPs) comprise one or many structural components of virions, except their genetic material. Thus, VLPs keep their structural properties of cellular recognition while being non-infectious. VLPs of Parvovirus B19 (B19V) can be produced by the heterologous expression of their structural proteins VP1 and VP2 in bacteria. These proteins are purified under denaturing conditions, refolded, and assembled into VLPs. Moreover, chimeric forms of VP2 have been constructed to harbor peptides or functional proteins on the surface of the particles without dropping their competence to form VLPs, serving as presenting nanoparticles. The in-vitro assembly approach offers exciting possibilities for the composition of VLPs, as more than one chimeric form of VP2 can be included in the assembly stage, producing multifunctional VLPs. Here, the heterologous expression and in-vitro assembly of B19V structural proteins and their chimeras are reviewed. Considerations for the engineering of the structural proteins of B19V are also discussed. Finally, the construction of multifunctional VLPs and their future potential as innovative medical tools are examined.

Keywords: enzyme nanocarriers; nanobiotecnology; nanomedicine; parvovirus-like particles; protein engineering.

Figure 1

(A) Structure of the B19V VLP conformed by the VP2 protein (PDB 1S58). In orange is highlighted a monomer of the capsid. The 2-fold (circle), 3-fold (triangle), and 5-fold (pentamer) axes are indicated. (B) Structure of the monomer of VP2 in the capsid of B19V colorized by B-factors. The upper right side corresponds to the external surface of the VLPs and the bottom left side corresponds to the internal surface of the particle. The N-terminus corresponds to residue 19. (C) B-factor graph for the Cα of the B19V capsid. The most prominent values are highlighted with reddish bars and correspond to the external surface loops shown in panel B. The arbitrary limit of 175 Ų in the B-factor for loop engineering is shown.

Figure 2

Potential applications of the B19V VLPs. It is possible to present antigens of transmissible or non-transmissible diseases on the surfaces of the particles. VLPs can be loaded with drugs, peptides, proteins, or nucleic acids. Enzymes or proteins can also be presented or immobilized on the surfaces of the VLPs. Functional peptides for cell tagging or for bioconjugation purposes can also be displayed on the surfaces of B19V VLPs. Bioconjugating peptides allow for these nanoparticles to be decorated with a wide variety of molecules with biotechnological applications. Two or more of these properties can be combined in a single particle, producing polyfunctional VLPs.