Characterization of clinical cases associated with porcine circovirus type 3: genetic analysis, frequency of detection and association with histologic lesions

Abstract

Porcine circovirus type 3 (PCV3) is a recently discovered porcine circovirus species, firstly identified in swine herds from the United States in the summer of 2015 via next generation sequencing (NGS). The objective of this thesis is to characterize clinical cases associated with PCV3, including investigating the genetic variability of PCV3 in the US shortly after its discovery, describing PCV3 detection frequency in veterinary diagnostic samples and investigating its association with clinical signs and histologic lesions.In Chapter 1, the current literature on PCV3 was reviewed. In Chapter 2, the genetic variability of PCV3 was investigated. We sequenced the whole PCV3 genome from seven samples obtained from swine herds in Iowa, Minnesota and North Carolina. Except for one pair of sequences that were from the same system, the DNA sequences of the genomes had 0.25-1.37% nucleotide differences at the whole genome level, 0.45-0.79% in open reading frame 1 (ORF1) and 0.31-2.4% in the ORF2. This was consistent with the genetic variability of PCV3 previously described in the US and worldwide. In a phylogenetic analysis, our PCV3 genomes along with other US PCV3 sequences clustered in multiple subgroups containing also global PCV3 references, indicating that the US sequences did not appear to have a recent common ancestor and therefore were most likely not the result of a recent introduction from other countries. In Chapter 3, the frequency of PCV3 and its association with clinical signs and lesions was investigated. We found PCR assay results were positive for PCV3 for 27% samples, 35% submissions, 38% sites and 81% states in a database of 730 diagnostic swine cases containing 2,177 samples. PCV3 was detected in multiple specimen types and in pigs of all ages and clinical presentations. Of 58 types of histologic lesions evaluated, we found that PCV3 detection was associated with myocarditis, cardiac vasculitis, and interstitial pneumonia in growing pigs. A high PCV3 detection rate was observed in aborted fetuses. In conclusion, results from this thesis indicate there was less than 2% genetic variation in US PCV3 genomes sequenced in the early years after its discovery, and US PCV3 clustered into different clades of global PCV3 references, suggesting that PCV3 was not a recent introduction into the US swine population. We also demonstrated that PCV3 was widespread in US swine herds. PCV3 detection was associated with myocarditis, cardiac vasculitis, and interstitial pneumonia in growing pigs, and PCV3 could be a cause of fetal death.