title: Recognition of the different structural forms of the capsid protein determines the outcome following infection with porcine circovirus type 2.
abstract: Porcine circovirus type 2 (PCV2) capsid protein (CP) is the only protein necessary for the formation of the virion capsid, and recombinant CP spontaneously forms virus-like particles (VLPs). Located within a single CP subunit is an immunodominant epitope consisting of residues 169 to 180 [CP(169-180)], which is exposed on the surface of the subunit, but, in the structural context of the VLP, the epitope is buried and inaccessible to antibody. High levels of anti-CP(169-180) activity are associated with porcine circovirus-associated disease (PCVAD). The purpose of this study was to investigate the role of the immune response to monomer CP in the development of PCVAD. The approach was to immunize pigs with CP monomer, followed by challenge with PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV). To maintain the CP immunogen as a stable monomer, CP(43-233) was fused to ubiquitin (Ub-CP). Size exclusion chromatography showed that Ub-CP was present as a single 33-kDa protein. Pigs immunized with Ub-CP developed a strong antibody response to PCV2, including antibodies against CP(169-180). However, only low levels of virus neutralizing activity were detected, and viremia levels were similar to those of nonimmunized pigs. As a positive control, immunization with baculovirus-expressed CP (Bac-CP) resulted in high levels of virus neutralizing activity, small amounts of anti-CP(169-180) activity, and the absence of viremia in pigs following virus challenge. The data support the role of CP(169-180) as an immunological decoy and illustrate the importance of the structural form of the CP immunogen in determining the outcome following infection.
authors.affiliation: Department of Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Trible
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Suddith
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Kerrigan
authors.forename: Ada G
authors.initials: AG
authors.lastname: Cino-Ozuna
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hesse
authors.forename: Raymond R R
authors.initials: RR
authors.lastname: Rowland
mesh_terms: D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D036022:Capsid Proteins / Q000378:metabolism*; D002850:Chromatography, Gel; D018173:Circoviridae Infections / Q000378:metabolism / Q000503:physiopathology*; D017925:Circovirus / Q000276:immunology / Q000378:metabolism*; D017931:DNA Primers; D007150:Immunohistochemistry; D009500:Neutralization Tests
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D017931:DNA Primers