p53 signaling modulation of cell cycle arrest and viral replication in porcine circovirus type 2 infection cells.
p53 signaling modulation of cell cycle arrest and viral replication in porcine circovirus type 2 infection cells.
复制标题
p53信号调节猪圆环病毒2型感染细胞的细胞周期停滞和病毒复制
DOI：
10.1186/s13567-016-0403-4
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发表时间：
2016-11-29
影响因子：
4.4
通讯作者：
Tong D
中科院分区：
文献类型：
--
作者：
Xu D;Du Q;Han C;Wang Z;Zhang X;Wang T;Zhao X;Huang Y;Tong D
猪圆环病毒2型（PCV2）是一种普遍存在于全球养猪业的病原体。既往研究表明PCV2感染通过上调p53诱导宿主细胞凋亡。为了进一步确定p53信号在PCV2感染过程中的调控作用，我们利用基因组编辑工具CRISPR/Cas9建立p53基因敲除的PK15细胞系，进一步研究p53在调节细胞周期和病毒复制中的作用。结果表明，PCV2感染在野生型PK15细胞中诱导了明显的S期积累，在p53基因突变细胞（813pk15p53 3m/m）中诱导了明显的S期积累，而在p53基因敲除细胞（148PK15p53−/−）中与模拟感染相比，没有诱导明显的S期积累。PCV2感染激活p53信号，上调p21、Cyclin E的表达，下调Cyclin A、CDK2的表达。然而，在p53缺陷细胞中，pcv2诱导的Cyclin A、CDK2和Cyclin E的变化被有效地逆转到基础水平。PCV2复制检测显示，与p53野生型细胞相比，不同同步处理后p53缺陷细胞（148PK15p533−/−）和p53突变细胞（813PK15p53m/m）的病毒ORF1基因组DNA减少。此外，感染后18 h， S期同步细胞释放的细胞中PCV2病毒基因组DNA和Cap蛋白水平高于G0/G1期或G2/M期同步细胞释放的细胞和非同步细胞释放的细胞。综上所述，本研究表明PCV2感染通过激活p53通路诱导S期积累，从而有利于病毒在宿主细胞中的复制。
Porcine circovirus type 2 (PCV2) is a ubiquitous pathogen in the swine industry worldwide. Previous studies have shown that PCV2 infection induces host cell apoptosis through up-regulation of p53. To further identify the regulatory roles of p53 signaling in the process of PCV2 infection, we established p53 gene knockout PK15 cell lines using the genomic editor tool CRISPR/Cas9, and further investigated the roles of p53 in modulating the cell cycle and viral replication in this study. The results show that PCV2 infection induced obvious S phase accumulation in wild-type PK15 cells and a compromised S phase accumulation in the p53 gene mutation cells (813PK15p53m/m), but did not induce obvious S phase accumulation in the p53 gene knockout cells (148PK15p53−/−) compared with the respective mock infection. PCV2 infection activated p53 signaling, up-regulated the expression of p21, Cyclin E, and down-regulated Cyclin A, CDK2. In p53 deficient cells, however, PCV2-induced changes in Cyclin A, CDK2, and Cyclin E were efficiently reversed to the basal levels. Detection of PCV2 replication showed decreased viral ORF1 genomic DNA in p53 deficient cells (148PK15p533−/−) and p53 mutated cells (813PK15p53m/m) compared with p53 wild-type cells after different synchronization treatment. Furthermore, PCV2 viral genomic DNA and Cap protein levels were higher in the cells released from S phase synchronized cells than in the cells released from the G0/G1 phase or G2/M phase-synchronized, or asynchronous cells after 18 h post-infection. Taken together, this study demonstrates that PCV2 infection induces S phase accumulation to favor viral replication in host cells through activation of the p53 pathway.
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影响因子：
56.9
作者：
Poon, B;Grovit-Ferbas, K;Chen, ISY
通讯作者：
Chen, ISY
影响因子：
5.4
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Ojala PM
影响因子：
3.7
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Huang Y;Xing N;Wang Z;Zhang X;Zhao X;Du Q;Chang L;Tong D
通讯作者：
Tong D
影响因子：
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