PFT-? inhibits gallid alpha herpesvirus 1 replication by repressing host nucleotide metabolism and ATP synthesis

文献类型： 外文期刊

第一作者： Xu, Li

作者： Xu, Li;Wang, Zhitao;Chen, Zhijie;Cui, Lu;Liu, Zheyi;Liang, Yumeng;Li, Xuefeng;Zhang, Yanhui;Liu, Shengwang;Li, Hai;Li, Hai

作者机构：

关键词： Alphaherpesviruses; Virus-host interactions; Virus replication;

PFT-alpha

; Nucleotide metabolism; ATP synthesis

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.246； 五年影响因子：3.565 ）

ISSN： 0378-1135

年卷期： 2022 年 269 卷

页码：

收录情况： SCI

摘要： Therapeutics targeting virus-host interactions have been considered promising strategies for treating herpesvirus infection. Our previous study on avian infectious laryngotracheitis virus (ILTV), an avian herpesvirus econom-ically important to the poultry industry worldwide, identified the small molecule Pifithrin-alpha (PFT-alpha) as a po-tential therapeutic agent. However, the underlying mechanisms of its antiviral function remain largely unknown. Using the ILTV-permissive chicken cell line LMH as the model, we found that PFT-alpha effectively suppressed the transcription and genome replication of ILTV and greatly reduced the level of infectious virions. Genome-wide transcriptome analysis revealed extensive repression of the metabolic processes of infected cells by PFT-alpha administration. Further metabolome assays of ILTV-infected cells using liquid chromatography coupled with mass spectrometry suggest host nucleotide metabolism and ATP synthesis as the key targets of PFT-alpha treatment during its repression of ILTV replication, which was experimentally supported by the reduced transcription of many key enzymes essential to nucleotide metabolism and ATP synthesis. The present study provides insights into the mechanisms by which PFT-alpha inhibits ILTV infection, which may increase the probability of successful clinical application of this molecule.

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