P53 maintains gallid alpha herpesvirus 1 replication by direct regulation of nucleotide metabolism and ATP synthesis through its target genes

文献类型： 外文期刊

第一作者： Xu, Li

作者： Xu, Li;Chen, Zhijie;Zhang, Yu;Cui, Lu;Liu, Zheyi;Li, Xuefeng;Liu, Shengwang;Li, Hai;Li, Hai

作者机构：

关键词： alphaherpesviruses; P53; PFT-alpha; virus-host interactions; virus replication

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：6.064； 五年影响因子：6.843 ）

ISSN：

年卷期： 2022 年 13 卷

页码：

收录情况： SCI

摘要： P53, a well-known tumor suppressor, has been confirmed to regulate the infection of various viruses, including chicken viruses. Our previous study observed antiviral effect of p53 inhibitor Pifithrin-alpha (PFT-alpha) on the infection of avian infectious laryngotracheitis virus (ILTV), one of the major avian viruses economically significant to the poultry industry globally. However, the potential link between this antiviral effect of PFT-alpha and p53 remains unclear. Using chicken LMH cell line which is permissive for ILTV infection as model, we explore the effects of p53 on ILTV replication and its underlying molecular mechanism based on genome-wide transcriptome analysis of genes with p53 binding sites. The putative p53 target genes were validated by ChIP-qPCR and RT-qPCR. Results demonstrated that, consistent with the effects of PFT-alpha on ILTV replication we previously reported, knockdown of p53 repressed viral gene transcription and the genome replication of ILTV effectively. The production of infectious virions was also suppressed significantly by p53 knockdown. Further bioinformatic analysis of genes with p53 binding sites revealed extensive repression of these putative p53 target genes enriched in the metabolic processes, especially nucleotide metabolism and ATP synthesis, upon p53 repression by PFT-alpha in ILTV infected LMH cells. Among these genes, eighteen were involved in nucleotide metabolism and ATP synthesis. Then eight of the 18 genes were selected randomly for validations, all of which were successfully identified as p53 target genes. Our findings shed light on the mechanisms through which p53 controls ILTV infection, meanwhile expand our knowledge of chicken p53 target genes.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序