Porcine circovirus 4 rescued from an infectious clone is replicable and pathogenic in vivo

Porcine circovirus 4 (PCV4) is a newly identified porcine circovirus in pigs, belonging to the Circoviridae family Circovirus genus. The virus was detected in all age groups and aborted foetuses. However, the virus has not been isolated from the field samples to date. In this study, PCV4 was successfully rescued from an infectious clone. The rescued PCV4 was replicable in PK-15 cells and piglets, which can be detected in almost all the collected samples of the challenge groups. No obvious clinical symptoms were observed in both sham- and PCV4-inoculated piglets during the whole experiment. However, visible pathological changes were found in several organs of the PCV4-inoculated piglets, indicating that rescued PCV4 was pathogenic in piglets. Furthermore, the viremia, PCV4-specific antibody, and upregulated cytokines/chemokines were also detected in the PCV4-inoculated groups, suggesting effective humoral and cellular immune responses were stimulated in response to the virus challenge. The PCV4 rescued in this study may provide the basis for preventing and controlling the disease, and vaccine development.