Epidemiological and molecular retrospective analysis of porcine circovirus 3 in the US grower-finisher herd.

Porcine circovirus type 3 (PCV3) was identified in 2016 and has since been associated with reproductive failure, multisystemic inflammation, and subclinical infection in swine. Numerous countries have retrospectively detected the presence of PCV3 before its first clinical description in 2016. The reported detection rate of PCV3 has varied from 6.5 to 84 % in pigs with various coinfections. Today, PCV3/PCV2 coinfection is commonly observed. However, the PCV3 prevalence and coinfection rate with PCV2 in the US swine industry had not been reported before 2016. The present study used serum samples from US grower finisher farms from 2000, 2006, and 2012 to determine the PCV3 and PCV3/PCV2 farm prevalence and geographical distribution, to evaluate the PCV3 evolutionary rate and selection pressure forces, and to identify structural and morphological changes in the Cap protein. Our findings revealed that PCV3 was endemic in the US swine industry before its first description in 2016. The PCV3 farm prevalence decreased from 47 % in 2000 to 22 % in 2012. The PCV3/PCV2 coinfection rate at the farm level was 47 % in 2000 and 39 % in 2006. After the introduction of PCV2 vaccines in 2006, the PCV3/PCV2 coinfection rate drastically declined to 3 % and 59 % of farms were negative for both PCV3 and PCV2 in 2012. From 13 PCV3 whole genome sequences, 12 sequences were clustered with PCV3a reference strain and one with the PCV3c subtype. From 28 PCV3 ORF2 sequences, PCV3a1 (1/28), PCV3a2 (4/28), PCV3a3 (19/28), PCV3b (2/28), and PCV3c (2/28) subtypes were obtained. ORF2 nucleotide identity ranged from 97.8 to 100 %. Diversifying selection occurred at amino acids 24 and 150 in 2006 and at amino acids 24 and 27 in 2012. Mutations A24V and R27K were common among all PCV3 subtypes in sequences identified in the present study and in reference sequences. Both the S77T and I150L mutation was common among sequences within the PCV3a2 subtype. The F104Y mutation lies within a predicted T-cell epitope and was present in sequences of the PCV3c, PCV3b, and PCV3a3 subtypes. Cap molecular modeling revealed that the structural folding of amino acids 24 and 27 changed from alpha helix to coiled in 2012 sequences. Thus, this study broadens current knowledge of PCV3's prevalence and molecular evolution in the US swine herd from 2000 to 2012.