Single amino acid mutations in the capsid switch the neutralization phenotype of porcine circovirus 2

Porcine circovirus 2 (PCV2) is the causative agent of porcine circovirus-associated diseases in pigs. Previously, it was demonstrated that mAbs 16G12, 38C1, 63H3 and 94H8 directed against the PCV2 capsid protein recognize PCV2 strains Stoon-1010 (PCV2a), 48285 (PCV2b), 1121 (PCV2a), 1147 (PCV2b) and II9F (PCV2b), but only neutralize Stoon-1010 and 48285. This points to the existence of two distinct PCV2 neutralization phenotypes: phenotype alpha (mAb recognition with neutralization; Stoon-1010 and 48285) and phenotype beta (mAb recognition without neutralization; 1121, 1147 and II9F). In the present study, amino acids that are important in determining the neutralization phenotype were identified in the capsid. Mutation of T at position 190 to A in strain 48285 (phenotype alpha) resulted in a capsid resembling that of strain 1147 (phenotype beta) and caused a loss of neutralization (switch from alpha to beta). Mutations of P at position 151 to T and A at position 190 to T in strain II9F (phenotype beta) resulted in a capsid resembling that of strain 48285 (phenotype alpha) and gave a gain of neutralization (switch from beta to alpha). Mutations of Tat position 131 to P and of E at position 191 to R in Stoon-1010 (phenotype alpha) changed the capsid into that of 1121 (phenotype beta) and reduced neutralization (switch from alpha to beta). This study demonstrated that single amino acid changes in the capsid result in a phenotypic switch from alpha to beta or beta to alpha.