Porcine circovirus type 2 (PCV2) is a ubiquitous pathogen in the swine industry worldwide. Previous studies have\nshown that PCV2 infection induces host cell apoptosis through up-regulation of p53. To further identify the regulatory\nroles of p53 signaling in the process of PCV2 infection, we established p53 gene knockout PK15 cell lines using\nthe genomic editor tool CRISPR/Cas9, and further investigated the roles of p53 in modulating the cell cycle and viral\nreplication in this study. The results show that PCV2 infection induced obvious S phase accumulation in wild-type\nPK15 cells and a compromised S phase accumulation in the p53 gene mutation cells (813PK15p53m/m), but did not\ninduce obvious S phase accumulation in the p53 gene knockout cells (148PK15p53âË?â??/âË?â??) compared with the respective\nmock infection. PCV2 infection activated p53 signaling, up-regulated the expression of p21, Cyclin E, and downregulated\nCyclin A, CDK2. In p53 deficient cells, however, PCV2-induced changes in Cyclin A, CDK2, and Cyclin E were\nefficiently reversed to the basal levels. Detection of PCV2 replication showed decreased viral ORF1 genomic DNA in\np53 deficient cells (148PK15p533âË?â??/âË?â??) and p53 mutated cells (813PK15p53m/m) compared with p53 wild-type cells after\ndifferent synchronization treatment. Furthermore, PCV2 viral genomic DNA and Cap protein levels were higher in the\ncells released from S phase synchronized cells than in the cells released from the G0/G1 phase or G2/M phase-synchronized,\nor asynchronous cells after 18 h post-infection. Taken together, this study demonstrates that PCV2 infection\ninduces S phase accumulation to favor viral replication in host cells through activation of the p53 pathway.
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