Abstract
Although porcine circovirus-like particles can function as a vector to carry foreign peptides into host cells, displaying foreign peptides on the surface of virus-like particles (VLPs) remains challenging. In this study, a plateau, consisting of the middle portion of Loop CD (MP-Lcd) from two neighboring subunits of PCV2 capsid protein (Cap), was identified as an ideal site to insert various foreign peptides or epitopes and display them on the surface of PCV2 VLPs. One of the goals of this work is to determine if the surface pattern of this plateau can be altered without compromising the neutralizing activity against PCV2 infections. Therefore, biological roles of MP-Lcd regarding VLPs assembly, cell entry, and antigenicity were investigated to determine whether this was a universal site for insertion of foreign functional peptides. Three-dimensional (3D) structure simulations and mutation assays revealed MP-Lcd was dispensable for PCV2 Cap assembly into VLPs and their entry into host cells. Notably, substitution of MP-Lcd with a foreign peptide, caused surface pattern changes around two-fold axes of PCV2 VLPs based on 3D structure simulation, but was not detrimental to VLPs assembly and cell entry. Moreover, this substitution had no adverse effect on eliciting neutralizing antibodies (NAbs) against PCV2 infection in pigs. In conclusion, MP-Lcd of the PCV2 Cap was a promising site to accommodate and display foreign epitopes or functional peptides on the surface of PCV2 VLPs. Furthermore, chimeric VLPs (cVLPs) would have potential as bivalent or multivalent vaccines and carriers to deliver functional peptides to target cells.
Highlights
Porcine circovirus (PCV), a member of the Circovirus genus in the Circoviridae family, has a small, single-stranded and circular DNA genome
Based on structural features and absence of middle portion of Loop CD (MP-Lcd) in PCV3 capsid protein (Cap), together with previous study that an epitope derived from PPRSV GP5 was successfully inserted Loop CD (Hu et al, 2016). we inferred that MP-Lcd was an optimal target site for inserting foreign peptides and displaying them on the surface of the PCV2 capsid
Since the nuclear localization signal (NLS) at the NT of the PCV2 Cap is not required for virus-like particles (VLPs) assembly (Khayat et al, 2011), several PCV2 chimeric VLPs (cVLPs) were successfully prepared by replacing the NLS with a T-cell epitope, B-cell epitope, or a T-cell epitope conjugated with a B-cell epitope of classical swine fever virus (CSFV)
Summary
Porcine circovirus (PCV), a member of the Circovirus genus in the Circoviridae family, has a small, single-stranded and circular DNA genome. There are two main genotypes, namely porcine circovirus type 1 (PCV1) and PCV2, both of which share high levels of nucleotide homology and a common genomic organization (Segales et al, 2013). PCV2 cVLPs Displays Foreign Peptides isolates, PCV2 is divided into four main subtypes (PCV2a, PCV2b, PCV2c, and PCV2d) (Franzo et al, 2015). A novel PCV genotype was identified (Phan et al, 2016; Palinski et al, 2017; Zhang et al, 2017) and temporarily designated PCV3, as its genomic DNA only shared ∼30% nucleotide identities with PCV1 and PCV2 (Palinski et al, 2017). Pathogenicity and potential lesions caused by PCV3 remain to be determined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
