Construction and in vivo characterization of an infectious clone of porcine circovirus type 3 from southwestern China

Porcine circovirus type 3 (PCV3) is an emerging viral pathogen associated with multi-systemic inflammation, porcine dermatitis and nephropathy syndrome, and reproductive failure, leading to substantial economic losses in the global swine industry. Although PCV3 has been widely detected in southwestern China, its pathogenic characteristics remain insufficiently understood. In this study, an infectious clone of the PCV3/SC/Sichuan-2023 strain was constructed using the pBluescript SK(+) backbone and subsequently employed to rescue the recombinant virus rPCV3. The recovered rPCV3 replicated efficiently in vitro and induced overt clinical manifestations and pathological lesions in piglets that closely recapitulated those observed under field conditions. Strong viral antigen signals were detected predominantly in the lungs and lymphoid tissues, confirming distinct tissue tropism. Similarly, rPCV3 infection elicited significant upregulation of pro-inflammatory cytokines, reflecting the immune dysregulation characteristic of natural infection. These results demonstrate that rPCV3 reproduces essential pathogenic features observed during experimental infection and aligns closely with reports from field strains. Furthermore, the established infectious clone provides a robust reverse-genetics platform for virus rescue, stable propagation in PK-15 cells, and comprehensive in vitro and in vivo characterization, facilitating future investigations into PCV3 pathogenesis and the development of effective control strategies in southwestern China.IMPORTANCEPorcine circovirus type 3 (PCV3) is widely prevalent in pig populations; however, its biological characteristics and pathogenic mechanisms remain incompletely understood. In this study, we generated a full-length infectious clone of a field-derived PCV3 strain. We demonstrated that the rescued virus faithfully reproduces critical aspects of natural infection, including robust replication, distinct tissue tropism, and cytokine dysregulation in piglets. These findings provide valuable experimental tools and novel insights into PCV3 pathogenesis, supporting enhanced disease control strategies and future vaccine development.